Increase in Plasma Oxidized Phosphatidylcholines (OxPCs) in Patients Presenting With ST-Elevation Myocardial Infarction (STEMI)

Objective: ST-segment Elevation Myocardial Infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using percutaneous coronary intervention (PCI), a large percentage of myocardial cells die after reperfusion which is recognized as ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPCs) are a group of oxidized lipids generated through non-enzymatic oxidation and have pro-inflammatory properties. This study aimed to examine the roles of OxPCs in a clinical setting of myocardial I/R.Methods: Blood samples were collected from STEMI patients at presentation prior to primary PCI (PPCI) (Isch) and at 4 time-points post-PPCI, including 2 h (R-2 h), 24 h (R-24 h), 48 h (R-48 h), and 30 days (R-30 d) post-PPCI. As controls, blood samples were collected from patients with non-obstructive coronary artery disease after diagnostic coronary angiography. Aspiration thrombectomy was also performed in selected STEMI patients. High-performance lipid chromatography-electrospray mass spectrometry (LC-MS/MS) was used for OxPCs analysis.Results: Twenty-two distinct OxPC species were identified and quantified in plasma samples in patients presenting with STEMI. These compounds were categorized as fragmented and non-fragmented species. Total levels of OxPCs did not significantly differ between Isch and control groups. However, total levels of fragmented OxPCs increased significantly in the ischemic period compared with controls (Isch: 4.79 ± 0.94, Control: 1.69 ± 0.19 ng/μl of plasma, P < 0.05). Concentrations of non-fragmented OxPCs had significant reductions during ischemia compared to the control group (Isch: 4.84 ± 0.30, Control: 6.6 ± 0.51 ng/μl, P < 0.05). Levels of total OxPCs in patients with STEMI were not significantly different during reperfusion periods. However, fragmented OxPCs levels were elevated at 48 h post-reperfusion and decreased at 30 days following MI, when compared to R-2 h and R-24 h time points (Isch: 4.79 ± 0.94, R-2 h: 5.33 ± 1.17, R-24 h: 5.20 ± 1.1, R-48 h: 4.18 ± 1.07, R-30 d: 1.87 ± 0.31 ng/μl, P < 0.05). Plasma levels of two fragmented OxPCs, namely, POVPC and PONPC were significantly correlated with peak creatine kinase (CK) levels (P < 0.05). As with plasma levels, the dominant OxPC species in coronary aspirated thrombus were fragmented OxPCs, which constituted 77% of total OxPC concentrations.Conclusion: Biologically active fragmented OxPC were elevated in patients presenting with STEMI when compared to controls. PONPC concentrations were subsequently increased after PPCI resulting in reperfusion. Moreover, levels of POVPC and PONPC were also associated with peak CK levels. Since these molecules are potent stimulators for cardiomyocyte cell death, therapeutics attenuating their activities can result in a novel therapeutic pathway for myocardial salvage for patients undergoing reperfusion therapy.

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Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01058.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. H1679-H1686 ◽

Cited By ~ 13

Author(s):

Frederic Treguer ◽

Erwan Donal ◽

Sophie Tamareille ◽

Nehmat Ghaboura ◽

Geneviève Derumeaux ◽

...

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Rat Model ◽

Speckle Tracking ◽

Ischemia Reperfusion ◽

Control Group ◽

Myocardial Salvage ◽

Speckle Tracking Imaging ◽

Triphenyltetrazolium Chloride ◽

Conventional Echocardiography

A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion. Rats were randomly assigned to one of three groups: myocardial infarction (MI)-control group, 45 min ischemia followed by 24 h of reperfusion; MI-EPO group, similar surgery with a single bolus of EPO administered at the onset of reperfusion; and sham-operated group. Short-axis two-dimensional echocardiography was performed after reperfusion. Global radial (GSr) and circumferential (GScir) strains were compared with infarct size and TEMI assessed after triphenyltetrazolium chloride staining. As a result, ejection fraction, shortening fraction, GSr, and GScir significantly correlated to infarct size, whereas only GSr and GScir significantly correlated to TEMI. EPO significantly decreased infarct size (30.8 ± 3.5 vs. 56.2 ± 5.7% in MI-control, P < 0.001) and TEMI (0.37 ± 0.05 vs. 0.77 ± 0.05 in MI-control, P < 0.001). None of the conventional echocardiography parameters was significantly different between the MI-EPO and MI-control groups, whereas GSr was significantly higher in the MI-EPO group (29.1 ± 4.7 vs. 16.4 ± 3.3% in MI-control; P < 0.05). Furthermore, GScir and GSr appeared to be the best parameters to identify a TEMI >0.75 24 h after reperfusion. In conclusion, these findings demonstrate the usefulness of speckle tracking imaging in the early evaluation of a cardioprotective strategy in a rat model of ischemia-reperfusion.

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Ultrasound assessment of heart remodelling affected by therapeutic hypothermia and MSC on myocardial infarction model

Український радіологічний та онкологічний журнал ◽

10.46879/ukroj.3.2020.222-240 ◽

2020 ◽

Vol 28 (3) ◽

pp. 222-240

Author(s):

M. O. Chyzh ◽

A. O. Manchenko ◽

A. V. Trofimova ◽

I. V. Belochkina

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Ejection Fraction ◽

Stroke Volume ◽

Therapeutic Hypothermia ◽

Left Coronary Artery ◽

Left Ventricular ◽

Control Group ◽

Normal Range ◽

Allogeneic Mscs

Background. Late seeking medical advice, limited number of cardiac surgery hospitals and conservative treatment, which does not seem to be always efficacious, trigger the search for new, more effective mode therapy of acute myocardial infarction (MI). Recently, mesenchymal stromal cells (MSCs) have come into sharp focus of scientists due to the prospects for clinical use. On the other hand, multicenter studies have proved that therapeutic hypothermia (TH) has neuro- and cardioprotective effects, and it is administered as one of the urgent methods in providing primary health care. Purpose. Providing and analyzing ultrasonography (US) of rat hearts with experimental MI in order to determine the nature of heart remodelling under combined use of TH and introducing allogeneic MSCs. Materials and methods. The study involved 90 outbred white rats weighing 240–270 g. Myocardial infarction was reproduced by ligating the descending branch of the left coronary artery on the border of the upper and middle third of the vessel. Therapeutic hypothermia was performed in a cold chamber, 60 minutes long. The local skin temperature of the neck area was maintained at +4 оC, while the rectal and tympanic temperature decreased to + 25 оC. A suspension of allogeneic cryopreserved MSCs of the placenta with a concentration of 1.2 × × 106 cells/ml was administered once intravenously through v. saphena magna. Heart sonography was carried out by means of «Сономед 500» («СПЕКТРОМЕД», Russia) ultrasound scanner in B- and M-mode using a linear sensor 7.5L38 with frequency of 7.5 MHz. Results and discussion. The control group with experimental MI showed significantly suppressed function of the left ventricle (LV). It resulted in decreasing stroke volume (SV) and cardiac output (CO) and on the whole indicated reduced ejection fraction (EF) to 46.04 %, that was 35 % less than the corresponding normal range. According to the values of relative wall thickness (RWT) and left ventricular mass (LVM) on day 7 and day 30 after ligating the left coronary artery, LV remodelling was proceeding via eccentric mode of LV alteration. Therapeutic hypothermia was not able to completely stop the pathophysiological processes associated with coronary ligation. EF was not significantly different from the control group, and was 51.08 ± ± 2.68 %. On day 7 of the experiment, heart remodelling in this group was proceeding according to the normal geometry model, and on day 30 – according to the eccentric model. In spite of the volume overload causing post-infarction extension of the left ventricular cavity, in the group with applying MSCs, on day 7 there was a compensatory increase of the stroke volume, 1.8 times over compared to the group with normal range values and 2.3 over compared to the control group. The ejection fraction was 17 % less than the normal range, but statistically significantly higher than the corresponding indicator of the control group of this observation period. Heart remodelling after applying allogeneic MSCs associated with MI at all stages of observation was proceeding by eccentric LV hypertrophy. Аfter therapeutic hypothermia and applying MSCs associated with experimental myocardial infarction on day 7 and day 30, the group recorded the best values of echo params of LV anatomical structures, indicating no dilatation along with occuring moderate myocardial hypertrophy. The ejection fraction showed the best outcome, i. e. 58.78 %, while LV remodelling was minimal, occurring according to normal heart geometry. Conclusions. Applying echocardiography in rats is a very informative diagnosis method which makes it possible to describe the type of structural and functional remodelling of the myocardium associated infarction at early and late observation stages. The ultrasound study showed that the closest to the normal range was the group of animals exposed to therapeutic hypothermia and MSC transplantation. According to LVM and RWT values, in the rats of that group on day 7 and day 30 of the experiment, LV remodelling was characterized by normal geometry.

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The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

Ain-Shams Journal of Anesthesiology ◽

10.1186/s42077-021-00174-2 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Maha Sadek El Derh ◽

Samar Mohamed Abdel Twab ◽

Mohamed Elgouhary

Keyword(s):

Coronary Artery ◽

Cardiac Index ◽

Reperfusion Injury ◽

Troponin I ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Control Group ◽

Myocardial Infarct Size ◽

Off Pump ◽

Coronary Artery Revascularization

Abstract Background Off pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease. Methods We divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration. Results This study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO. Conclusions This study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

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Cytokine status in patients with myocardial infarction as a possible predictor of coronary atherosclerosis severity

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2020-2316 ◽

2020 ◽

Vol 19 (3) ◽

pp. 2316

Author(s):

O. V. Khlynova ◽

E. A. Shishkina ◽

N. I. Abgaryan

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Coronary Atherosclerosis ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

C Reactive Protein ◽

Reactive Protein ◽

Coronary Artery Atherosclerosis ◽

Tnf Α ◽

Atherosclerosis Severity

Aim. To study the association of cytokine status with coronary atherosclerosis severity in patients with myocardial infarction (MI).Material and methods. Between 11.2018 and 07.2019, 92 patients hospitalized with MI in Perm Clinical Cardiology Dispensary were included in the study. The control group consisted of 23 patients with stable coronary artery disease. In addition to the standard examination, enzyme-linked immunosorbent assay was used to determine the levels of interleukins (IL)-6, -10, tumor necrosis factor alpha (TNF-α), C-reactive protein.Results. Significant increase in plasma IL-6, TNF-α and C-reactive protein levels in MI patients compared with the control group. The increase in the concentration of IL-6, TNF-α, as well as the IL-6/IL-10 ratio occurs in proportion to coronary atherosclerosis severity. A direct correlation of Gensini score with IL-6, TNF-α, and IL-6/IL-10 ratio was established.Conclusion. Further study of cytokine profile parameters in MI patients will help a clearer understanding pathogenesis of coronary artery atherosclerosis. An increase in concentrations of IL-6, TNF-α, and IL-6/IL-10 ratio is associated with an increase in coronary atherosclerosis severity and can be used in practice for its prediction.

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Abstract 2419: Left Ventricle Function Preservation by a Novel Synthetic Hydrogel Injection in Myocardial Infarction Rabbit

Circulation ◽

10.1161/circ.118.suppl_18.s_722-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Xiaoyan Li ◽

Xuejun Jliang ◽

Tao Wang ◽

Taol Lin ◽

Congxin Huang ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Coronary Artery ◽

Left Ventricle ◽

Ethylene Glycol ◽

Control Group ◽

Coronary Artery Ligation ◽

Poly Ethylene Glycol ◽

Infarcted Myocardium ◽

Poly Ethylene

Myocardial infarction and the subsequent heart failure remain among the world’s prominent health challenges. Other studies have demonstrated that bio-derived materials improve cardiac function after implantation for angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricle (LV) function through its prevention of paradoxical systolic bulging. Infarction was induced in rabbit myocardium by coronary artery ligation. In sham-operated rabbits (n = 5), a suture was tied loosely around the left anterior descending coronary artery without ligating it. 7 dayslater, 100μl α-cyclodextrin (CD) solution and 100μl poly (ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly (ethylene glycol)(MPEG-PCL-MPEG) solution (n = 7) was injected simultaneously through Duploject applicator into the infarcted myocardium. Solid hydrogel matrix formed by linear MPEG-PCL-MPEG polymer threading into the cavities of the α-cyclodextrin after mixing. Injection of phosphate buffered saline (PBS) served as controls (n = 7). 28 days after the treatments, histological analysis indicated that injection of hydrogel prevented scar expansion and wall thinning compared with group ( P < 0.05) without more microvessel density in infarcted myocardium ( P = 0.70).By echocardiography, LV ejection fraction was significantly greater in the hydrogel group (56.09 ± 8.42%) than the control group (37.26 ± 6.36%, P = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 ± 0.33 cm and 1.74 ± 0.30cm in the control group, respectively. Smaller LV end-diastolic diameter (1.61 ± 0.26cm, P = 0.005) and smaller end-systolic diameter (1.17 ± 0.23cm, P = 0.001) were found in the hydrogel group. These results suggest that α-CD/MPEG-PCL-MPEG hydrogel injection could serve structural and mechanical support of an injured LV replacing some of the functions of the damaged ECM and thus prevented paradoxical motion serves, which may eventually lead to LV remodeling and dilation prevention. Our study should initiate further experimental and clinical studies exploring potential approaches to the treatment of postinfarction heart failure.

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Abstract 442: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis via Mir122 Induction

Circulation Research ◽

10.1161/res.119.suppl_1.442 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Jingyuan Li ◽

Negar Motayagheni ◽

Neusha Barakati ◽

Mansoureh Eghbali

Keyword(s):

Coronary Artery ◽

Infarct Size ◽

Reperfusion Injury ◽

Microarray Analysis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Late Pregnancy ◽

Control Group ◽

Myocardial Infarct Size ◽

Microrna Microarray

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.

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P3391Cholesterol crystals in culprit coronary artery with acute myocardial infarction and their relation to myocardial salvage

European Heart Journal ◽

10.1093/eurheartj/ehz745.0267 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Nunohiro ◽

S Kuwasaki ◽

T Fukushima ◽

S Furudono ◽

H Suenaga ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

At Risk ◽

Coronary Artery ◽

Infarct Size ◽

Myocardial Salvage ◽

Area At Risk ◽

Risk Area ◽

Contrast Enhanced ◽

Delayed Enhancement Imaging

Abstract The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. However, little is known about CCs and myocardial salvage in the Acute myocardial infarction (AMI) patients. This study aimed to evaluate the association between the existence of CCs at the site of culprit coronary artery and myocardial salvage index (MSI).To investigate, we applied the diagnostic resources of Optical Coherence Tomography (OCT). Methods This study included 53 AMI patients (90% with STEMI) who underwent primary PCI within 24h of onset. 53 STEMI patients underwent magnetic resonance imaging (CMR) of 5th days and 3 months after PCI. Infarct size was measured on delayed-enhancement imaging, and area at risk was quantified on T2-weighted imaging. MSI was calculated as [area at risk − infarct size] × 100/area at risk. 3 months CMR with contrast-enhanced imaging of late gadolinium enhancement-LGE. Patients were divided 2 groups according to the existence of CCs at the site of culprit coronary artery. Results CCs occurs in 26 of 53 (49%). Acute 5th days risk area (13.5±4.1 vs 12.6±4.9, P=0.48) and 3months infarct size (5.3±3.5 vs 7.0±3.2, P=0.066) were not significant between CCs and no CCs group. But salvage index were significantly lower in patients with CCs group (47.7±17.5% vs 60.1±20.2%, P=0.021) Conclusion Salvage index in patients that CCs were found by the OCT analysis, remain low after AMI. This study demonstrates the potential correlation between the myocardial salvage and vulnerable morphological features of culprit lesion to the presence of CCs with AMI patients.

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Neutrophil Phenotypes in Coronary Artery Disease

Journal of Clinical Medicine ◽

10.3390/jcm9051602 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1602

Author(s):

Patrick Maréchal ◽

Julien Tridetti ◽

Mai-Linh Nguyen ◽

Odile Wéra ◽

Zheshen Jiang ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Plasma Levels ◽

Stable Coronary Artery Disease ◽

St Elevation Myocardial Infarction ◽

Multivariable Logistic Regression Analysis ◽

Coronary Syndrome ◽

St Elevation ◽

Artery Disease

Clinical evidence indicates that innate immune cells may contribute to acute coronary syndrome (ACS). Our prospective study aimed at investigating the association of neutrophil phenotypes with ACS. 108 patients were categorized into chronic stable coronary artery disease (n = 37), unstable angina (UA) (n = 19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n = 25), and ST-Elevation Myocardial Infarction (STEMI) (n = 27). At the time of inclusion, blood neutrophil subpopulations were analysed by flow cytometry. Differential blood cell count and plasma levels of neutrophilic soluble markers were recorded at admission and, for half of patients, at six-month follow-up. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio than stable and UA patients (p < 0.0001), which normalized at six-month post-MI. Atypical low-density neutrophils were detected in the blood of the four patient groups. STEMI patients were characterized by elevated percentages of band cells compared to the other patients (p = 0.019). Multivariable logistic regression analysis revealed that plasma levels of total myeloperoxidase was associated with STEMI compared to stable (OR: 1.434; 95% CI: 1.119–1.837; P < 0.0001), UA (1.47; 1.146–1.886; p = 0.002), and NSTEMI (1.213; 1.1–1.134; p = 0.0001) patients, while increased neutrophil side scatter (SSC) signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033–14.184; p = 0.045). Hence, changes in neutrophil phenotype are concomitant to ACS.

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PROLACTIN IN MAINTENANCE OF THE CORPUS LUTEUM OF EARLY PSEUDOPREGNANCY IN THE GOLDEN HAMSTER

Journal of Endocrinology ◽

10.1677/joe.0.0900145 ◽

1981 ◽

Vol 90 (2) ◽

pp. 145-150 ◽

Cited By ~ 7

Author(s):

K. H. HARRIS ◽

B. D. MURPHY

Keyword(s):

Single Dose ◽

Corpus Luteum ◽

Golden Hamster ◽

Peripheral Blood ◽

Plasma Levels ◽

Progesterone Level ◽

Control Group ◽

Blood Samples

The role of prolactin in the maintenance of the corpus luteum of pseudopregnancy was studied in the golden hamster. Nine groups of seven to fourteen animals each received 1 mg bromocriptine at 11.00 h on days 1, 2 or 3 of pseudopregnancy (three groups for each day). On each day of treatment with bromocriptine, one group of hamsters was injected with bovine prolactin 4 h before bromocriptine, and one group received prolactin 4 h before bromocriptine for three consecutive days following treatment with bromocriptine. One group received bromocriptine only. These nine groups were compared with a control group of animals given 0·85% saline instead of bromocriptine and prolactin. Peripheral blood samples were taken from all hamsters at 11.00 h on days 3, 4, 5 and 6 of pseudopregnancy and plasma levels of progesterone were determined by radioimmunoassay. Luteolysis, indicated by a decline in progesterone level by 24 or 48 h after treatment with bromocriptine, occurred in all hamsters given bromocriptine alone, whether it was administered on day 1, 2 or 3. Pretreatment with a single dose of prolactin did not mitigate the bromocriptine-induced fall in progesterone. In the majority of cases, pretreatment with prolactin plus daily doses of prolactin maintained the progesterone at levels not different from saline-treated hamsters. These data suggest that prolactin is a necessary luteotrophin during early pseudopregnancy without which luteolysis ensues.

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Comparison of Pharmacodynamic Effects and Plasma Levels of Oral and Rectal Ergotamine

Cephalalgia ◽

10.1046/j.1468-2982.1986.0602107.x ◽

1986 ◽

Vol 6 (2) ◽

pp. 107-111 ◽

Cited By ~ 8

Author(s):

PM Bülow ◽

JJ Ibraheem ◽

G Paalzow ◽

P Tfelt-Hansen

Keyword(s):

Crossover Study ◽

Strain Gauge ◽

Drug Combination ◽

Initial Dose ◽

Plasma Levels ◽

Biologically Active ◽

Blood Samples ◽

Rectal Dose ◽

And Control ◽

Ergotamine Tartrate

Plasma levels and the vasoconstrictive effect of 1 mg ergotamine tartrate given as tablets or suppositories were compared. In a crossover study, eight male volunteers received tablets or suppositories containing ergotamine in a drug combination (Anervan®) and, as a control, suppositories without ergotamine. Blood sampling and measurement of toe-arm systolic gradients with a strain-gauge technique were done for up to 6 h and again after 24 h and 48 h. Only 29 of 160 blood samples contained detectable (>0.1 mg/ml) amounts of ergotamine, and kinetic comparison could not be performed. Only ergotamine-containing suppositories caused a significant ( p < 0.008) decrease in toe-arm systolic gradient which was significantly different ( p < 0.003) from the effects of ergotamine tablets and control suppositories. Rectal ergotamine is thus more biologically active, for the factor used, than oral ergotamine. We suggest that a rectal dose of 1 mg ergotamine tartrate should be tried as the initial dose in the treatment of migraine attacks.

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