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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac hypertrophy is an adaptive response to an increased load imposed on the myocyte which allows the heart to perform increased work while maintaining normal myocardial fiber stress and shortening in systole. A deleterious consequence of pressure-overload hypertrophy is the prolongation of Ca(2+)-sensitive force inactivation (impaired myocardial relaxation) which is related to intrinsic alterations in cytosolic Ca2+ transport and reuptake in diastole. Additional factors appear to adversely modify myocardial relaxation in the hypertrophied heart, including the imposition of ischemia. There is also evidence that the expression and activity of the cardiac tissue renin angiotensin system (RAS) may be modified in the hypertrophied heart and contribute to diastolic dysfunction. Recent studies have demonstrated the presence of increased cardiac angiotensin converting enzyme (ACE) mRNA expression and activity in animal models of hypertrophy, including the aortic-banded rat with compensatory pressure-overload hypertrophy and rats with post-infarction remodeling. In the beating, isovolumic aortic-banded rat heart, the increased intracardiac activation of angiotensin I to II has been shown to be associated with a dose-dependent depression of diastolic relaxation. Preliminary studies suggest that the depression of diastolic function by angiotensin II in the hypertrophied heart can be prevented by the specific inhibition of cardiac ACE. In addition, the well-recognized susceptibility of the hypertrophied heart to severe ischemic diastolic dysfunction also appears to be favorably modified by the inhibition of cardiac ACE activity. The mechanisms responsible for the adverse effects of angiotensin II on diastolic relaxation in the hypertrophied heart are likely to be complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts. 133 63

The effects of early reperfusion were studied in closed-chest pigs subjected to either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during early reperfusion and electrophysiological stability after two weeks were assessed. Coronary artery occlusion durations of 3 hr and early reperfusion after 45 min were compared. The creatine phosphokinase levels in the coronary effluent were lower after early reperfusion (p less than 0.001). Moreover, in the early reperfusion group, the coronary sinus catecholamine and purine levels rose to higher values than in the 3 hr group. The plasma levels of catecholamines and the plasma renin activity increased rapidly but transiently at reperfusion in the 45 min group. Both the rate-pressure product and the heart rate were elevated at the end of the reperfusion period (p less than 0.001) in the 45 min group. Survival for two weeks was 3 out of 6 animals in the 3 hr group and 5 out of 8 in the 45 min group. In all but one surviving animal, sustained ventricular tachycardias were inducible by programmed stimulation. Abnormally low QRS amplitudes and delayed potentials were found in the signal-averaged electrocardiogram in the early reperfusion group only. In conclusion, early reperfusion causes a reduction of myocardial tissue damage, but simultaneously, neurohumoral parameters showed a greater activation of the sympathetic nervous system and the renin-angiotensin system apparently causing a deleterious increase in oxygen consumption. Therefore, this injurious component of early reperfusion might prevent the potentially beneficial effects of a reduced tissue damage on survival or late arrhythmias.
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PMID:Neurohumoral changes and the inducibility of ventricular tachycardias: effect of early reperfusion on the ischemic porcine myocardium. 135 23

Cardioprotection is a broad term; this short review deals with six aspects: 1. Secondary prevention of myocardial infarction (MI) has been shown for beta-blockers in both early and late intervention studies. Dihydropyridine calcium antagonists are associated with an excess incidence of coronary events, whereas non-dihydropyridines prevent reinfarction provided left ventricular (LV) function is adequate; dihydropyridines tend to increase heart rate and stimulate the sympathetic and renin-angiotensin systems. 2. Primary prevention of MI has been shown for beta-blockers in younger/middle-aged hypertensives but not in the elderly. Diuretics, by contrast, possibly increase the risk of coronary events in younger/middle-aged hypertensives but significantly reduce coronary events in older hypertensives. These results might be explained by the larger, noncompliant left ventricle of the elderly hypertensive, which, in the absence of overt ischemia, responds poorly to beta-blockade (further enlargement with increased wall stress and impaired coronary reserve), while diuretics have the opposite effect. Primary prevention of coronary events in patients with chronic angina is likely to occur with beta-blockers, while studies with calcium antagonists have shown a significant excess of coronary events. 3. Ischemic events occurring during the "vulnerable" period between 7 and 10 AM (when sympathetic activity is maximal) are significantly reduced by beta-blockers but not by calcium antagonists. 4. Stress-induced myocardial necrosis in humans is markedly reduced by beta-blockers. 5. Coronary risk factors, such as elevated blood lipids, hyperglycemia, and insulin resistance, are possibly adversely affected by diuretics and beta-blockers, with the former also increasing heart rate, plasma renin activity, and plasma catecholamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive drugs and cardioprotection. 136 81

In a blind, randomized study, the effects of perindopril, a nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were compared with those of placebo in a closed-chest pig model of myocardial infarction. In anesthetized pigs, myocardial ischemia and reperfusion were induced by inflation and deflation of a catheter balloon in the left anterior descending coronary artery (LAD), respectively. Thirty minutes after induction of ischemia and 15 min before reperfusion, a bolus injection of 0.06 mg/kg perindoprilat (n = 12), the active compound of perindopril, or placebo (n = 12) was administered in the pulmonary artery of these animals. After the acute phase of myocardial infarction, treatment with 12 mg/day perindopril or placebo was continued orally for 2 weeks. During the entire treatment period, 7 of 12 animals died in the placebo group versus 2 of 12 animals in the perindopril group (Fisher's exact test p less than 0.04). This beneficial effect of perindopril on mortality could not be attributed to salvage of myocardial tissue because the increases in creatine phosphokinase and coronary venous purine levels were similar in perindopril- and placebo-treated animals. Neither were there any significant between-treatment differences in the hemodynamic and (neuro)humoral parameters during the acute phase of myocardial infarction. The difference in mortality was observed within 24 h after myocardial infarction. Prevention of acute pump failure and, especially, life-threatening ventricular arrhythmias may explain this improvement in survival by perindopril. Retrospectively, logistic regression analysis showed that, irrespective of treatment, survival was inversely correlated to plasma renin activity (PRA) before induction of ischemia (r = -0.33; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of early angiotensin-converting enzyme inhibition in a pig model of myocardial ischemia and reperfusion. 137 22

Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.
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PMID:Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs. 145 81

The effects of combined alpha/beta adrenoceptor blockade and of beta-receptor/slow channel calcium blockade on systemic and pulmonary hemodynamics and on adrenergic activity were compared in two matched groups of men suffering from ischemic heart disease and grade 1 to 2 hypertension. They were studied at rest supine and during ischemia-inducing exercise in the seated posture using invasive percutaneous techniques. Sixteen patients received 200 mg labetalol as a single oral doses, 15 received 100 mg metoprolol plus 10 mg nifedipine. Both regimens reduced pressures in the systemic and pulmonary circulation under all conditions. At rest, stroke volume and cardiac output slightly decreased after labetalol and increased after metoprolol/nifedipine. During exercise the changes induced by the two regimens were virtually identical; heart rates and vascular resistances were reduced, stroke volume increased, cardiac output was not significantly changed. Plasma renin activity was lowered by labetalol, unchanged by metoprolol/nifedipine. Plasma adrenaline increased after metoprolol/nifedipine only, noradrenaline with both regimens. Both combinations significantly lowered stroke work and the rate pressure product and had similar beneficial effects on the onset and the duration of angina. It is concluded that both combinations significantly reduce blood pressures and attenuate or offset the potential adverse hemodynamic effects of beta-receptor blockade alone without loss but rather enhancement of antianginal efficacy.
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PMID:Acute effects of combined alpha/beta-adrenoceptor blockade v combined beta-receptor and slow channel calcium blockade in ischemic heart disease complicated by hypertension. Hemodynamic and adrenergic responses. 168 21

We have investigated the contribution of the renin-angiotensin system to the damage caused by 40-min global ischemia in the isolated rat heart. A converting enzyme inhibitor, enalaprilat (70 nM), an angiotensin II receptor antagonist, compound 89 (2 microM), and an inhibitor of rat renin, CGP 44099A (20 nM), given before ischemia reduced the median duration of ventricular fibrillation on reperfusion to a similar extent (5.53, 5.72, and 5.14 min, respectively, compared to 13.98 min in the control group) but had no effect on creatine phosphokinase release (22.2 +/- 2.6, 22.1 +/- 6.8, and 24.1 +/- 3.6, IU/30 min, respectively, compared to 19.9 +/- 1.9 IU/30 min) or recovery or left ventricular developed pressure (67 +/- 6, 73 +/- 7 and 71 +/- 6%, respectively, compared to 66 +/- 3% after 30 min reperfusion). The increase in coronary resistance and left ventricular diastolic pressure on reperfusion was not affected by any of the agents. All three agents also tended to reduce the duration of ventricular fibrillation when given only on reperfusion. We conclude that angiotensinogen is present in the rat heart and it is converted to angiotensin I by a renin or a renin-like aspartic proteinase. The angiotensin I is converted to angiotensin II by converting enzyme. The angiotensin II formed is an important mediator of postreperfusion ventricular fibrillation in the isolated rat heart but does not contribute to the reduction in mechanical function produced by global ischemia in this preparation.
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PMID:Involvement of the renin-angiotensin system in ischemic damage and reperfusion arrhythmias in the isolated perfused rat heart. 171 94

In an attempt to separate the cardiac effects of converting-enzyme (CE) inhibition from those on blood pressure, experiments were performed in rats and dogs with nonantihypertensive (subhypotensive) doses of the CE inhibitor ramipril. (a) Left ventricular hypertrophy: Rats with aortic constriction treated with a nonantihypertensive dose of ramipril (10 micrograms/kg/day) for 6 weeks showed the same prevention and regression of cardiac hypertrophy as groups receiving the antihypertensive dose of 1 mg/kg/day. Comparable results were obtained in animals treated for 1 year. (b) Ischemia-reperfusion injuries: In rats, subchronic oral administration of ramipril in a subhypotensive dose (10 micrograms/kg/day) prevented ex vivo postischemic reperfusion arrhythmias and improved cardiodynamic and metabolic parameters. Almost complete inhibition of cardiac CE was achieved with this low dose. (c) Acute myocardial infarction: Ramiprilat (40 ng/kg/min) was infused for 6 h into the left coronary artery of anesthetized dogs with a ligation of the descending branch of this artery. This route and the low dose were chosen to achieve local cardiac effects without affecting systemic hemodynamics. Ramiprilat significantly reduced the infarct area expressed as a percentage of the area at risk. This cardioprotective effect of ramiprilat was mimicked by bradykinin and abolished by coadministration of a bradykinin antagonist. Thus, factors beyond blood pressure reduction and load changes may add to the cardiovascular benefits of CE inhibitors. This may indicate local (cardiac) paracrine and/or autocrine effects of the renin-angiotensin system and/or participation of kinins.
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PMID:Experimental cardiovascular benefits of angiotensin-converting enzyme inhibitors: beyond blood pressure reduction. 172 38

ANF is totally filtrated by the kidney and is degradated in the brush border of the tubuli. In an experimental transplant model in dogs excretion of ANF is investigated after a cold ischemia period of 48 h and HTK-protection. The ANF-renin-antagonism was of interest respectively. The experiments demonstrated that the filtration in the glomeruli and the function of the endopeptidases in the brush border is normal after a cold ischemia period of 48 and HTK-protection. There is a linear correlation between the concentration of ANF in the renal vein and the aorta. An antagonism of ANF and renin could not be found. ANF is discussed as an additional ischemia parameter in renal transplantation.
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PMID:[Clearance behavior of the kidney in relation to ANF in the autologous dog transplantation model]. 183 13

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.
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PMID:[Possibilities of ACE inhibitor therapy in acute myocardial ischemia]. 186 31


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