Abstract 149: Zoniporide Combined with α-Methylnorepinephrine Promotes Greater Hemodynamic Stability than Either Agent Alone During Chest Compression in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lorissa Lamoureux ◽  
Herbert K Whitehouse ◽  
Jeejabai Radhakrishnan ◽  
Raúl J Gazmuri
Keyword(s):  
Chest Compression ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Blood Flows ◽  
Compression Time ◽  
Sprague Dawley Rats ◽  
Sodium Hydrogen Exchanger ◽  
Ventricular Distensibility ◽  
Over Time

Background: We have reported in animal models of cardiac arrest that sodium hydrogen exchanger-1 (NHE-1) inhibition - by attenuating reperfusion injury - helps preserve left ventricular distensibility yielding higher forward blood flows during chest compression. Others have reported that α-methylnorepinephrine (α-MNE) - a selective peripheral α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effect that intensifies myocardial ischemia. We examined in a rat model of VF the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE during CPR, expecting to elicit a vasopressor effect (α-MNE) that is better maintained over time because of ZNP. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes. Chest compression was then initiated, gradually increasing the depth of compression (maximum 17 mm) to attain an aortic diastolic pressure of 28 mmHg by the end of minute 2, maintaining such level for the remaining 6 minutes of chest compression, time at which defibrillation was attempted. The rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest compression with the investigators blind to the assignment. Results: The ratio between the aortic diastolic pressure and depth of compression (Figure) was higher - as expected - in rats that received α-MNE(+) given its vasopressor effect. The effect, however, was not maintained and declined over time; but to a significantly lesser degree in rats that also received ZNP; i.e., α-MNE(+)/ZNP(+) group. Conclusions: The findings support a favorable interaction between α-MNE and ZNP; the first prompting needed peripheral vasoconstriction - likely with less concomitant myocardial injury - and the latter preserving left ventricular distensibility, which combined enhance the hemodynamic efficacy of chest compression.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen

2007 ◽  
Vol 293 (1) ◽  
pp. H590-H598 ◽  
Author(s):  
Eduard I. Dedkov ◽  
Wei Zheng ◽  
Lance P. Christensen ◽  
Robert M. Weiss ◽  
Florence Mahlberg-Gaudin ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Perfusion ◽  
Transforming Growth Factor ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Coronary Reserve ◽  
Osmotic Pumps ◽  
Sprague Dawley Rats

We tested the hypothesis that chronically reducing the heart rate in infarcted middle-aged rats using ivabradine (IVA) would induce arteriolar growth and attenuate perivascular collagen and, thereby, improve maximal perfusion and coronary reserve in the surviving myocardium. Myocardial infarction (MI) was induced in 12-mo-old male Sprague-Dawley rats, which were then treated with either IVA (10.5 mg·kg−1·day−1; MI + IVA) or placebo (MI) via intraperitoneal osmotic pumps for 4 wk. Four weeks of IVA treatment limited the increase in left ventricular end-diastolic pressure and the decrease in ejection fraction but did not affect the size of the infarct, the magnitude of myocyte hypertrophy, or the degree of arteriolar and capillary growth. However, treatment reduced interstitial and periarteriolar collagen in the surviving myocardium of MI + IVA rats. The reduced periarteriolar collagen content was associated with improvement in maximal myocardial perfusion and coronary reserve. Although the rates of proliferation of periarteriolar fibroblasts were similar in the MI and MI + IVA groups, the expression levels of the AT1 receptor and transforming growth factor (TGF)-β1 in the myocardium, as well as the plasma level of the ANG II peptide, were lower in treated rats 14 days after MI. Therefore, our data reveal that improved maximal myocardial perfusion and coronary reserve in MI + IVA rats are most likely the result of reduced periarteriolar collagen rather than enhanced arteriolar growth.

scholarly journals Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

2016 ◽  
Vol 311 (2) ◽  
pp. H337-H346 ◽  
Author(s):  
Hong Zheng ◽  
Xuefei Liu ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricle ◽  
Cardiac Function ◽  
Renal Denervation ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Sprague Dawley Rats

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/d t to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/d t (by 71%) and −dP/d t (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

Chronic arteriovenous shunt: evaluation of a model for heart failure in rat

1979 ◽  
Vol 236 (5) ◽  
pp. H698-H704 ◽  
Author(s):  
S. F. Flaim ◽  
W. J. Minteer ◽  
S. H. Nellis ◽  
D. P. Clark
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Plasma Catecholamine ◽  
Sprague Dawley ◽  
Blood Flows ◽  
Aortocaval Shunt ◽  
Circulatory Effects ◽  
High Output Heart Failure ◽  
Postsurgical Recovery

A model for high output heart failure (HCO) was developed in male, Sprague-Dawley rats using an abdominal aortocaval shunt equal to 50% of total cardiac output (CO) with 2 mo of postsurgical recovery. The model was evaluated by analysis of hemodynamics, peripheral blood flows (BF) (radioactive microspheres), and plasma catecholamine levels as well as mass and fluid content of organs. In HCO, CO and left ventricular end-diastolic pressure were increased with significant left and right ventricular hypertrophy. Mean blood pressure (BP) was unchanged, but pulse BP was increased in HCO. BF to skeletal muscle, cutaneous, and some splanchnic regions was reduced to HCO, whereas BF to the cerebral, coronary, and renal beds was protected. Plasma epinephrine and norepinephrine levels were significantly elevated in HCO suggesting enhanced sympathetic as well as adrenal catecholamine release. Tissue analysis indicated altered circulatory status secondary to HCO in liver, kidney, spleen, and lung. The results indicate that this model will be a relevant tool for studies of the circulatory effects of heart failure.

Intracellular EDEMA does not adversely affect the ability to cryopreserve intact hearts

1993 ◽  
Vol 51 ◽  
pp. 278-279
Author(s):  
CL Hastings ◽  
RD Carlton ◽  
FG Lightfoot ◽  
AF Tryka
Keyword(s):  
Cell Injury ◽  
Median Sternotomy ◽  
Left Ventricular ◽  
Ventricular Free Wall ◽  
Hypoxic Cell ◽  
Free Wall ◽  
Sprague Dawley ◽  
Left Ventricular Free Wall ◽  
Sprague Dawley Rats

The earliest ultrastructural manifestation of hypoxic cell injury is the presence of intracellular edema. Does this intracellular edema affect the ability to cryopreserve intact myocardium? To answer this guestion, a model for anoxia induced intracellular edema (IE) was designed based on clinical intraoperative myocardial preservation protocol. The aortas of 250 gm male Sprague-Dawley rats were cannulated and a retrograde flush of Plegisol at 8°C was infused over 90 sec. The hearts were excised and placed in a 28°C bath of Lactated Ringers for 1 h. The left ventricular free wall was then sliced and the myocardium was slam frozen. Control rats (C) were anesthetized, the hearts approached by median sternotomy, and the left ventricular free wall frozen in situ immediately after slicing. The slam frozen samples were obtained utilizing the DDK PS1000, which was precooled to -185°C in liguid nitrogen. The tissue was in contact with the metal mirror for a dwell time of 20 sec, and stored in liguid nitrogen until freeze dry processing (Lightfoot, 1990).

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

scholarly journals Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5006
Author(s):  
Pema Raj ◽  
Karen Sayfee ◽  
Mihir Parikh ◽  
Liping Yu ◽  
Jeffrey Wigle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Additive Effects ◽  
Sprague Dawley ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Sprague Dawley Rats ◽  
And Function ◽  
Neutrophil Gelatinase

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.

Blood flow in normal and denervated muscle during exercise in conscious rats

1988 ◽  
Vol 255 (6) ◽  
pp. H1509-H1515 ◽  
Author(s):  
M. D. Delp ◽  
R. B. Armstrong
Keyword(s):  
Blood Flow ◽  
Muscular Activity ◽  
Sprague Dawley ◽  
Blood Flows ◽  
Sprague Dawley Rats ◽  
Mechanical Factors ◽  
Denervated Muscles ◽  
Gastrocnemius Muscles ◽  
Low Intensity Exercise ◽  
Hyperemic Response

The purpose of this study was to test the hypothesis that extrinsic mechanical factors, i.e., the dynamic shortening and lengthening imposed on a muscle during limb movements and the rhythmic compressions as surrounding muscles contract and relax, contribute to the initial muscle hyperemia during locomotion in conscious male Sprague-Dawley rats. Soleus and lateral head of gastrocnemius muscles were surgically denervated in one hindlimb several hours before exercise to remove 1) local metabolic vasodilator effects, 2) vasoconstrictor or vasodilatory influences mediated through sympathetic postganglionic fibers, and 3) intrinsic mechanical pumping. Blood flow was measured with radioactive microspheres during preexercise and at 30 s and 5 min of exercise in rats walking at 15 m/min or a motor-driven treadmill. Glycogen concentrations were also measured as an indicator of muscular activity to verify the denervation. Blood flows to control muscles in the normal limb were similar to previously reported values during preexercise and exercise. Denervation, however, decreased preexercise blood flow (69–88%) to muscle composed predominantly of oxidative fibers and increased flow (53%) to muscle composed predominantly of glycolytic fibers. During exercise, blood flow to denervated muscles either remained unchanged or decreased. These data suggest that extrinsic mechanical factors do not significantly contribute to the initial hyperemic response at the onset of low-intensity exercise in normal muscle.

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

2002 ◽  
Vol 282 (4) ◽  
pp. H1197-H1205 ◽  
Author(s):  
Michael J. Cox ◽  
Harpreet S. Sood ◽  
Matthew J. Hunt ◽  
Derrick Chandler ◽  
Jeffrey R. Henegar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blot Analysis ◽  
Diastolic Pressure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Cardiac Relaxation

The hypothesis is that chronic increases in left ventricular (LV) load induce oxidative stress and latent matrix metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide (NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V fistula, 2) A-V fistula + Nic, 3) sham operated, 4) sham + Nic, and 5) control (unoperated); n = 6 rats/group. After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed, and LV tissue homogeneates were prepared. A-V fistula caused an increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of malondialdehyde (MDA; a marker of oxidative stress) was 6.60 ± 0.23 ng/mg protein and NO was 6.87 ± 1.21 nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 ± 2.5 nmol/l and decreased MDA to 3.54 ± 0.34 ng/mg protein ( P= 0.005). Zymographic levels of MMP-2 were increased, as were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation. Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload.

Dietary carbohydrates modify cardiac myosin isoenzyme profiles of semistarved rats

1989 ◽  
Vol 256 (4) ◽  
pp. R976-R981
Author(s):  
G. S. Morris ◽  
R. E. Herrick ◽  
K. M. Baldwin
Keyword(s):  
Food Restriction ◽  
Systemic Blood Pressure ◽  
Left Ventricular ◽  
Cardiac Myosin ◽  
Dietary Carbohydrates ◽  
Sprague Dawley ◽  
Myosin Isoenzyme ◽  
Sprague Dawley Rats ◽  
Serum T3

Although food restriction reduces the relative expression of the rodent cardiac myosin isoenzyme V1, the contribution of accompanying metabolic changes to the induction and maintenance of this isoenzyme shift remains unknown. Hence, this study was undertaken to determine the role of carbohydrate (CHO) utilization in the regulation of cardiac myosin isoenzyme distribution in food-restricted rats. Female Sprague-Dawley rats received either a mixed diet (55% of calories as CHO, M) or a high-carbohydrate diet (75% of calories as CHO, HC). Additional animals in each dietary group received daily injections of triiodothyronine (T3; 0.075 microgram/100 microM + T3, HC + T3). Three weeks of food restriction reduced left ventricular Ca2+-activated myofibrillar adenosinetriphosphatase activity by 24% and the relative amount of the myosin V1 isoenzyme by 57% in the M group relative to free-eating controls (P less than 0.05). In contrast, these measures were reduced by only 9 and 21%, respectively, in the HC group. Administration of T3 exerted no apparent effect on V1 expression, regardless of diet. Furthermore, the increased expression of V1 in both HC and HC + T3 groups occurred independently of changes in several measures of thyroid status including serum T3 levels, O2 consumption, heart rate, and systemic blood pressure. These results further suggest that metabolic factors, specifically those associated with CHO utilization, can influence cardiac myosin isoenzyme expression.

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