Acetaminophen in the Post-ischemia Reperfused Myocardium

2002 ◽  
Vol 227 (11) ◽  
pp. 1031-1038 ◽  
Author(s):  
Roseli Golfetti ◽  
Knox VanDyke ◽  
Tyler Rork ◽  
Norell Spiler ◽  
Gary Merrill
Keyword(s):  
Creatine Kinase ◽  
Uric Acid ◽  
Myocardial Ischemia ◽  
Left Ventricular ◽  
The Other ◽  
Low Flow ◽  
Coronary Perfusion ◽  
Treatment Groups ◽  
Anti Oxidant ◽  
Reperfused Myocardium

Acetaminophen was administered acutely at the onset of reperfusion after 20 min of low-flow, global myocardial ischemia in isolated, perfused guinea pig hearts (Langendorff) to evaluate its influence in the postischemia, reperfused myocardium. Similarly prepared hearts were treated with vehicle or with uric acid (another phenol for comparison). Functionally, acetaminophen-treated hearts (0.35 mM) achieved significantly greater recovery during reperfusion. For example, left ventricular developed pressures at 40 min reperfusion were 38 ± 3, 27 ± 3, and 20 ± 2 in the presence of acetaminophen (P < 0.05, relative to the other two groups), vehicle, and uric acid, respectively. Coronary perfusion pressures and calculated coronary vascular resistances, in the acetaminophen-treated hearts, were significantly lower at the same time (e.g., coronary perfusion pressures in the three groups, respectively, were 40 ± 2 [P < 0.05], 51 ± 3, and 65 ± 12 mm Hg). Under baseline, control conditions, creatine kinase ranged from 12–15 units/liter in the three groups. It increased to 35–40 units/liter (P < 0.05) during ischemia but was significantly reduced by acetaminophen during reperfusion (e.g., 5.3 ± 0.8 units/liter at 40 min). Oxidant-mediated chemiluminescence in all three treatment groups during baseline conditions and ischemia was similar (i.e., approximately 1.5–2.0 min for peak luminescence to reach its half maximal value). It took significantly more time during reperfusion for the oxidation of luminol in the presence of acetaminophen (>20 min, P < 0.05) than in its absence (3–8 min in uric acid- and vehicle-treated hearts). These results suggest that administration of acetaminophen (0.35 mM), at the onset of reperfusion, provides anti-oxidant–mediated cardioprotection in the postischemia, reperfused myocardium.

Chronically Administered Acetaminophen and the Ischemia/Reperfused Myocardium

2003 ◽  
Vol 228 (6) ◽  
pp. 674-682 ◽  
Author(s):  
R. Golfetti ◽  
T. Rork ◽  
G. Merrill
Keyword(s):  
Creatine Kinase ◽  
Tap Water ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Low Flow ◽  
Control Group ◽  
Coronary Perfusion ◽  
In Vitro Production

Male and female Hartley strain guinea pigs weighing 280 ± 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion protocol. Our objective was to compare and contrast ventricular function, coronary circulation, and selected biochemical and histological indices in the two treatment groups. Left ventricular developed pressure in the early minutes of reperfusion was significantly greater in the presence of acetaminophen, e.g., at 1 min, 40 ± 4 vs 21 ± 3 mmHg ( P < 0.05). Coronary perfusion pressure was significantly less from 3 to 40 min of reperfusion in the presence of acetaminophen. Creatine kinase release in vehicle-treated hearts rose from 42 ± 14 (baseline) to 78 ± 25 units/liter by the end of ischemia. Corresponding values in acetaminophen-treated hearts were 36 ± 8 and 44 ± 14 units/liter. Acetaminophen significantly ( P < 0.05) attenuated release of creatine kinase. Chemiluminescence, an indicator of the in vitro production of peroxynitrite via the in vivo release of superoxide and nitric oxide, was also significantly attenuated by acetaminophen. Electron microscopy indicated a well-preserved myofibrillar ultrastructure in the postischemic myocardium of acetaminophen-treated hearts relative to vehicle-treated hearts (e.g., few signs of contraction bands, little or no evidence of swollen mitochondria, and well-defined light and dark bands in sarcomeres with acetaminophen; opposite with vehicle). We conclude that chronic administration of acetaminophen provides cardioprotection to the postischemic, reperfused rodent myocardium.

Endogenous endothelin-1 impairs endothelium-dependent relaxation after myocardial ischemia and reperfusion

1994 ◽  
Vol 267 (5) ◽  
pp. H1833-H1841 ◽  
Author(s):  
J. M. Hagar
Keyword(s):  
Myocardial Ischemia ◽  
Control Release ◽  
Microvascular Dysfunction ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Developed Pressure ◽  
Eta Receptor Antagonist

Endothelin (ET)-1 is produced in response to myocardial ischemia and reperfusion. It is a potent constrictor of coronary resistance vessels and may therefore contribute to myocardial injury and postischemic microvascular dysfunction. Isolated buffer-perfused rabbit hearts, under conditions of constant flow and isovolumic contraction, underwent 60 min of global ischemia and 60 min of reperfusion after pretreatment with selective ETA receptor antagonist BQ-123 (10(-7) M) in perfusate, exogenous ET-1 (10(-11) M), or control. Release of ET increased significantly at 20 and 60 min of reperfusion. BQ-123 did not enhance the recovery of left ventricular developed pressure or coronary perfusion pressure, whereas exogenous ET tended to worsen them. Cumulative creatine kinase release over 20 min of reperfusion did not differ significantly between groups. Maximum endothelium-dependent dilation to acetylcholine (ACh) was initially 62 +/- 6, 71 +/- 6, and 63 +/- 8% (SE) of U-46619-induced preconstriction in control, BQ-123-, and ET-treated hearts. At 20 min of reperfusion it was 37 +/- 5, 73 +/- 9, and 22 +/- 5%, and at 60 min of reperfusion it was 35 +/- 7, 79 +/- 6, and 22 +/- 3% (P < 0.001 for BQ-123 vs. control at 20 min and P < 0.0001 at 60 min). Endothelium-independent dilation to nitroglycerin was unaltered by ischemia and reperfusion. Neither BQ-123 alone nor a 1-h infusion of ET (10(-10) M) altered the response to ACh in nonischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion

2001 ◽  
Vol 280 (6) ◽  
pp. H2631-H2638 ◽  
Author(s):  
G. Merrill ◽  
P. McConnell ◽  
K. Vandyke ◽  
S. Powell
Keyword(s):  
Hydroxyl Radicals ◽  
Spin Trap ◽  
Constant Pressure ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Left Ventricular ◽  
Low Flow ◽  
Mammalian Myocardium ◽  
Antioxidant Mechanisms ◽  
Reperfused Myocardium

Acetaminophen is a phenol with antioxidant properties, but little is known about its actions on the mammalian myocardium and coronary circulation. We studied isolated, perfused guinea pig hearts, and tested the hypothesis that acetaminophen-treated hearts would be protected during ischemia-reperfusion. Acetaminophen concentrations in the range of 0.3–0.6 mmol/l caused modest but significant ( P< 0.05) coronary vasoconstriction and positive inotropy. The effects were more brisk during constant pressure perfusion than during constant flow. During 20 min of low-flow, global myocardial ischemia and 40 min of reperfusion, hearts treated with acetaminophen retained or recovered a greater percentage of left ventricular function than hearts treated with vehicle. Myofibrillar ultrastructure appeared to be preserved in the reperfused myocardium with acetaminophen. By using chemiluminescence and spin-trap methodologies, we investigated acetaminophen-mediated antioxidant mechanisms to help explain the cardioprotection. The burst of hydroxyl radicals seen between 0 and 10 min of reperfusion was significantly attenuated ( P < 0.05) by acetaminophen but not by vehicle. The 3-morpholinosydnominine (SIN-1) generation of peroxynitrite and its oxidative interaction with luminol to produce blue light during ischemia-reperfusion was also blocked by acetaminophen. Our results show that acetaminophen provides significant functional and structural protection to the ischemic-reperfused myocardium, and the mechanism of cardioprotection seems to involve attenuation of the production of both hydroxyl radicals and peroxynitrite.

scholarly journals Hemodynamic Instability during Dialysis: The Potential Role of Intradialytic Exercise

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Scott McGuire ◽  
Elizabeth Jane Horton ◽  
Derek Renshaw ◽  
Alofonso Jimenez ◽  
Nithya Krishnan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Physiological Response ◽  
Hemodynamic Instability ◽  
Left Ventricular ◽  
Haemodynamic Instability ◽  
Coronary Perfusion ◽  
Intradialytic Hypotension ◽  
Cardiovascular Morbidity And Mortality ◽  
Intradialytic Exercise ◽  
Acute Physiological Response

Acute haemodynamic instability is a natural consequence of disordered cardiovascular physiology during haemodialysis (HD). Prevalence of intradialytic hypotension (IDH) can be as high as 20–30%, contributing to subclinical, transient myocardial ischemia. In the long term, this results in progressive, maladaptive cardiac remodeling and impairment of left ventricular function. This is thought to be a major contributor to increased cardiovascular mortality in end stage renal disease (ESRD). Medical strategies to acutely attenuate haemodynamic instability during HD are suboptimal. Whilst a programme of intradialytic exercise training appears to facilitate numerous chronic adaptations, little is known of the acute physiological response to this type of exercise. In particular, the potential for intradialytic exercise to acutely stabilise cardiovascular hemodynamics, thus preventing IDH and myocardial ischemia, has not been explored. This narrative review aims to summarise the characteristics and causes of acute haemodynamic instability during HD, with an overview of current medical therapies to treat IDH. Moreover, we discuss the acute physiological response to intradialytic exercise with a view to determining the potential for this nonmedical intervention to stabilise cardiovascular haemodynamics during HD, improve coronary perfusion, and reduce cardiovascular morbidity and mortality in ESRD.

Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia

1992 ◽  
Vol 263 (5) ◽  
pp. H1390-H1396 ◽  
Author(s):  
I. Woditsch ◽  
K. Schror
Keyword(s):  
Nitric Oxide ◽  
Myocardial Ischemia ◽  
Protective Factor ◽  
Specific Activity ◽  
Coronary Perfusion Pressure ◽  
Protective Role ◽  
Low Flow ◽  
Coronary Perfusion ◽  
Early Reperfusion ◽  
Endogenous Nitric Oxide

Nitric oxide (NO) and prostacyclin (PGI2) were determined in effluents of Langendorff-perfused rabbit hearts subjected to 2 h of global low-flow ischemia and subsequent reperfusion. PGI2 release [6-oxo-prostaglandin (PG) F1 alpha] was significantly enhanced during early reperfusion and remained elevated. NO formation was reduced during ischemia but did increase substantially during reperfusion. Indomethacin (3 microM) significantly suppressed ischemia-related 6-oxo-PGF1 alpha and NO release. This was accompanied by severely diminished myocardial recovery. NG-nitro-L-arginine (L-NNA) (100 microM) suppressed NO generation without major effects on 6-oxo-PGF1 alpha generation and cardiac dysfunction but with a remarkable increase in coronary perfusion pressure. These effects of L-NNA were antagonized by L-arginine, whereas the effects of indomethacin were not. There was a substantial loss of creatine kinase specific activity from reperfused ischemic hearts, which was further aggravated by indomethacin but not by L-NNA. These data demonstrate a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia, which also involves preservation of NO generation. Endogenous NO appears to be important for local regulation of coronary flow.

Influence of metabolic substrate on rat heart function and metabolism at different coronary flows

1991 ◽  
Vol 261 (3) ◽  
pp. H741-H750 ◽  
Author(s):  
D. Burkhoff ◽  
R. G. Weiss ◽  
S. P. Schulman ◽  
R. Kalil-Filho ◽  
T. Wannenburg ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Volume ◽  
High Energy ◽  
Left Ventricular ◽  
Low Flow ◽  
Coronary Perfusion ◽  
Metabolic Substrate ◽  
Work Related ◽  
The Difference ◽  
Developed Pressure

The influence of metabolic substrate on contractile strength, myocardial oxygen consumption (MVO2), high- and low-energy phosphate levels, and intracellular pH were determined in isovolumically contracting isolated rat hearts perfused with solutions containing either glucose or hexanoate at both high and low coronary perfusion pressures (CPP). Contractile strength was not significantly influenced by substrate at a CPP of 80 mmHg. As coronary flow was decreased, developed pressure measured at a fixed left ventricular volume (LVV) was lower during hexanoate than glucose perfusion. The relationship between MVO2 and mechanical work determined at a CPP of 80 mmHg over a range of LVVs was shifted upward in a parallel manner when substrate was switched from glucose to hexanoate. The MVO2-work relationship measured at a fixed LVV but over a range of coronary flows (7-20 ml/min) was also parallel shifted upward on switching from glucose to hexanoate. Basal MVO2 was greater during hexanoate than glucose perfusion by an amount that accounted for two-thirds the total increase in MVO2 observed between the substrates under unloaded beating conditions. The remainder of the difference was attributed to increased energy requirements for excitation-contraction coupling. Inorganic phosphate concentrations increased more and phosphocreatine concentrations decreased more during low-flow conditions (3 ml/min) when hearts were perfused with hexanoate compared with glucose. Thus hexanoate decreases myocardial efficiency compared with glucose in large part by increasing non-work-related oxygen demands. This inefficiency impacts adversely on contractile strength and high-energy phosphate concentrations at low coronary flows.

Increased monocyte to HDL cholesterol ratio in vitamin B12 deficiency: is it related to cardiometabolic risk?

2020 ◽  
pp. 1-8
Author(s):  
Sanem Kayhan ◽  
Nazli Gulsoy Kirnap ◽  
Mercan Tastemur
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Uric Acid ◽  
Vitamin B12 ◽  
Cardiometabolic Risk ◽  
Vitamin B12 Deficiency ◽  
Left Ventricular ◽  
Cardiometabolic Risk Factors ◽  
B12 Deficiency ◽  
Deficiency Group

Abstract. Vitamin B12 deficiency may have indirect cardiovascular effects in addition to hematological and neuropsychiatric symptoms. It was shown that the monocyte count-to-high density lipoprotein cholesterol (HDL-C) ratio (MHR) is a novel cardiovascular marker. In this study, the aim was to evaluate whether MHR was high in patients with vitamin B12 deficiency and its relationship with cardiometabolic risk factors. The study included 128 patients diagnosed with vitamin B12 deficiency and 93 healthy controls. Patients with vitamin B12 deficiency had significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP), MHR, C-reactive protein (CRP) and uric acid levels compared with the controls (median 139 vs 115 mmHg, p < 0.001; 80 vs 70 mmHg, p < 0.001; 14.2 vs 9.5, p < 0.001; 10.2 vs 4 mg/dl p < 0.001; 6.68 vs 4.8 mg/dl, p < 0.001 respectively). The prevalence of left ventricular hypertrophy was higher in vitamin B12 deficiency group (43.8%) than the control group (8.6%) (p < 0.001). In vitamin B12 deficiency group, a positive correlation was detected between MHR and SBP, CRP and uric acid (p < 0.001 r:0.34, p < 0.001 r:0.30, p < 0.001 r:0.5, respectively) and a significant negative correlation was detected between MHR and T-CHOL, LDL, HDL and B12 (p < 0.001 r: −0.39, p < 0.001 r: −0.34, p < 0.001 r: −0.57, p < 0.04 r: −0.17, respectively). MHR was high in vitamin B12 deficiency group, and correlated with the cardiometabolic risk factors in this group, which were SBP, CRP, uric acid and HDL. In conclusion, MRH, which can be easily calculated in clinical practice, can be a useful marker to assess cardiovascular risk in patients with vitamin B12 deficiency.

Vergleich von Belastungs- EKG und Radionuklid- Ventrikulographie bezüglich des Nachweises einer Myokardischämie bei isolierten Stenosen des Ramus interventricularis anterior

1988 ◽  
Vol 27 (02) ◽  
pp. 57-62
Author(s):  
R. Standke ◽  
R. P. Baum ◽  
S. Tezak ◽  
D. Mildenberger ◽  
F. D. Maul ◽  
...  
Keyword(s):  
Heart Disease ◽  
Left Ventricular Ejection Fraction ◽  
Myocardial Ischemia ◽  
Ejection Fraction ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Global Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Exercise Ecg

21 patients with LAD-stenoses of at least 70% and 21 patients with LAD- stenoses and additional intramural anterior wall infarctions were studied. 20 patients without heart disease or after successful transluminal coronary angioplasty and 18 patients with intramural anterior wall infarction after successful transluminal dilatation of the LAD (remaining stenosis maximal 30%) served as controls. The normal range of global and regional left ventricular ejection fraction response to exercise was defined based on the data of 25 further patients without relevant coronary heart disease. Thus, a decrease in global ejection fraction and regional wall motion abnormalities were judged pathological. All patients were comparable with respect to age, ejection fraction at rest and work load. Myocardial ischemia could be detected by the exercise ECG in 81 % of all patients without infarction and in 71 % of patients with infarction. The corresponding values for global left ventricular ejection fraction were 76% and 81 %, respectively, and for regional ejection fraction 95% in both groups. No false-positive exercise ECGs were observed in the healthy controls and 2 (11 %) in the corresponding group with intramural infarction. The global ejection fraction was pathological in 1 (5%) healthy subject without infarction and in 3 (17%) corresponding patients with infarction. Sectorial analysis revealed 5 and 22%, respectively. Our findings suggest that the exercise ECG has a limited sensitivity to detect myocardial ischemia in patients with isolated LAD-stenoses and intramural myocardial infarction. Radionuclide ventriculography yields pathological values more often; however, false-positive results also occur more frequently.

New Hybrid Method for Left Ventricular Ejection Fraction Assessment from Radionuclide Ventriculography Images

2020 ◽  
Vol 16 ◽  
Author(s):  
Halima Dziri ◽  
Mohamed Ali Cherni ◽  
Dorra Ben Sellem
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Positive Predictive Value ◽  
Roc Curve ◽  
Radionuclide Ventriculography ◽  
Left Ventricular ◽  
The Other ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Background: In this paper, we propose a new efficient method of radionuclide ventriculography image segmentation to estimate the left ventricular ejection fraction. This parameter is an important prognostic factor for diagnosing abnormal cardiac function. Methods: The proposed method combines the Chan-Vese and the mathematical morphology algorithms. It was applied to diastolic and systolic images obtained from the Nuclear Medicine Department of Salah AZAIEZ Institute.In order to validate our proposed method, we compare the obtained results to those of two methods of the literature. The first one is based on mathematical morphology, while the second one uses the basic Chan-Vese algorithm. To evaluate the quality of segmentation, we compute accuracy, positive predictive value and area under the ROC curve. We also compare the left ventricle ejection fraction estimated by our method to that of the reference given by the software of the gamma-camera and validated by the expert, using Pearson’s correlation coefficient, ANOVA test and linear regression. Results and conclusion: Static results show that the proposed method is very efficient in the detection of the left ventricle. The accuracy was 98.60%, higher than that of the other two methods (95.52% and 98.50%). Likewise, the positive predictive value was the highest (86.40% vs. 83.63% 71.82%). The area under the ROC curve was also the most important (0.998% vs. 0.926% 0.919%). On the other hand, Pearson's correlation coefficient was the highest (99% vs. 98% 37%). The correlation was significantly positive (p<0.001).

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