Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diltiazem, a calcium channel blocking agent, has potent cardiovascular effects that are directly related to its influence on vascular smooth muscle, ventricular myocardium, and specialized conducting tissue. It causes coronary and peripheral vasodilation, has a negative chronotropic and dromotropic effect, and little to no negative inotropic effect in patients with normal ventricular function. Diltiazem has potential use in a wide variety of cardiovascular disorders. It has been shown extremely effective in relieving the coronary artery spasm associated with variant angina. When compared with nitrates in patients with exertional angina, diltiazem has similar efficacy. Preliminary work indicates it will have a therapeutic role in the treatment of unstable angina. Because of its ability to improve the balance between myocardial oxygen supply and demand and reduce cellular injury secondary to ischemia, it is likely that diltiazem will be of benefit in the treatment of acutely ischemic myocardium during cardiopulmonary bypass and possibly acute myocardial infarction. It has proven efficacy in treating re-entrant supraventricular tachycardia. Adverse effects are seen in less than 5% of patients, indicating that it is well tolerated.
 ...
PMID:The use of diltiazem hydrochloride in cardiovascular disorders. 676 99

The effect of diltiazem on the contractile and vascular responses to 2 min of total occlusion and reperfusion was investigated in isolated blood-perfused canine papillary muscle preparations. Diltiazem, in doses (3 and 10 micrograms/min) that increased coronary blood flow but did not change developed tension and maximum rate of tension development (dT/dt) in papillary muscle before occlusion, attenuated tension development between 40 and 120 sec of ischemia. At-60 sec postocclusion, developed tension was at 36 +/- 4, 37 +/- 5 and 44 +/- 4% below preocclusion levels for 3, 10 and 100 micrograms/min of diltiazem, respectively (nondiltiazem treated = 24 +/- 3%). The dT/dt increased to 22 +/- 6% above preocclusion value during ischemia in nondiltiazem-treated preparations. This was blocked by diltiazem in a dose-dependent fashion. Propranolol and nitroprusside did not modify the developed tension and the increase in dT/dt of the papillary muscle during occlusion. On reperfusion, an overshoot in developed tension to 22 +/- 4% above preocclusion level was observed. This was significantly reduced by diltiazem and propranolol but not by nitroprusside. Diltiazem inhibited the maximal peak reactive hyperemia response after 2 min of occlusion by 30 to 38%. Both propranolol and nitroprusside did not change this response. The results show that diltiazem selectively depresses the inotropic state of the ischemic myocardium and suggest that a diltiazem-induced reduction in myocardial oxygen consumption during ischemia may contribute to the protection of ischemic myocardium and the reduction in reactive hypermia response in the ischemic heart.
 ...
PMID:Studies on mechanisms of diltiazem-induced protection of the ischemic myocardium: selective myocardial depressant action of diltiazem on an ischemic isolated blood-perfused canine papillary muscle preparation. 684 4

Characteristics of the temporal elevation of diastolic tension, produced by ischemia-reperfusion in isolated and paced Langendorff's hearts of guinea pigs, were studied. The elevation of diastolic tension corresponded with an elevation of left ventricular end diastolic pressure after a short ischemic period in the isovolumic heart. These phenomena were thought to be a result of incomplete relaxation. The degree of the elevation of diastolic tension depended upon the duration of ischemic period (3-10 min). This elevation was reproducible in one preparation; nearly the same changes were obtained in a second trial after 35 min of reperfusion when the ischemic period was within 5 min. An increment in the pacing rate to 150% of the first trial value doubled the elevation of diastolic tension by the second 5 min ischemia. Inhibition of glycolytic flux by iode acetic acid augmented the elevation after 3 min of ischemia. In addition, 5 min of ischemia with iode acetic acid caused contracture and recovery was slight. On the other hand, either lowering the Ca2+ concentration in the perfusing solution to a half the normal value, or treatment with Ca2+ antagonists (such as diltiazem), reduced the elevation of diastolic tension significantly. Diltiazem also suppressed the increment in elevation produced by a high pacing rate. It can be concluded that the temporal elevation of diastolic tension during reperfusion reflects the ischemic failure of the heart. This change is presumably due to intracellular Ca2+ overload or accumulation. In addition, since ischemic changes were reproducible in this preparation, it is a useful model for estimating the effects of drugs on the ischemic heart.
 ...
PMID:Ischemia-reperfusion induced elevation of diastolic tension in the isolated guinea pig heart and the effects of calcium antagonists. 685 62

The calcium channel blocker, diltiazem, has been studied in the same model used for evaluation of cold blood-potassium cardioplegia. Six dogs (Group 1) had one hour of myocardial ischemia with topical ice (myocardial temperature, 7 degrees +/- 2 degrees C) after coronary perfusion with 200 ml of cold blood (5 degrees +/- 1 degree C) containing diltiazem, 400 micrograms per kilogram of body weight. Seven dogs (Group 2) had two hours of ischemia after perfusion with 200 ml of cold blood containing 200 micrograms/kg and reperfusion every 30 minutes with 100 ml of cold blood and diltiazem, 100 micrograms/kg. Baseline studies were repeated after rewarming and 40 minutes of reperfusion. No inotropic agents or calcium were used. Heart rate, peak systolic pressure, velocity of the contractile element, peak + rate of rise of left ventricular pressure (dP/dt), peak - dP/dt, dP/dt over common peak isovolumic pressure, left ventricular compliance and stiffness, and heart water were unchanged in Group 1. In Group 2, heart rate slowed (p less than 0.025) and compliance decreased (p less than 0.02). In both groups, coronary vascular resistance declined (p less than 0.001) and recovery of adenosine triphosphate (p less than 0.001), adenosine diphosphate (p less than 0.025), and the adenosine pool (p less than 0.001) was impaired. Ultrastructure was well preserved, but myofibrillar lesions were noted in Group 2. Diltiazem cardioplegia was associated with good functional recovery, but there was impairment of high-energy phosphate metabolism.
 ...
PMID:Cold blood-diltiazem cardioplegia. 706 65

Open heart surgery under aortic cross-clamping is often required, but coronary reperfusion injury after release of aortic cross-clamping is unavoidable irrespective of applications of various protective methods to the myocardium. The anterior descending branch of the left coronary artery of mongrel adult dogs was occluded for 2 hours and then reperfused. The protective effects of intra-aortic balloon pumping (IABP) and of a calcium antagonist "diltiazem hydrochloride" (diltiazem) on the decreased reperfusion of ischemic, border and normal areas were examined by measuring the regional myocardial blood flow (RMBF) using a radioactive microsphere method. Diltiazem could increase significantly the RMBF in the border area. IABP induced a significant increase in the RMBF of the same area more than Diltiazem, with the increase in the endocardial layer tending to be superior to that in the epicardial layer. The results suggested that diltiazem is very effective for reducing the coronary reperfusion injury. It is also suggested that IABP is even more effective than diltiazem because it increases the RMBF significantly and, moreover, has a tendency to increase the blood flow in the endocardial layer which is poor in collateral vessels and thus vulnerable to ischemia.
 ...
PMID:Effect of intra-aortic balloon pumping and calcium antagonist for reducing coronary reperfusion injury. 721 95

The protective effects of diltiazem, a calcium channel blocker, were studied in isolated, blood-perfused cat hearts subjected to 60 or 90 min of global ischemia, followed by reperfusion of 60 or 120 min, respectively. Ischemia-induced alterations of left ventricular (LV) developed pressure (DP) and compliance, measured with an intraventricular fluid-filled latex balloon, were correlated with respiratory activity in vitro of mitochondria isolated from ischemic-reperfused LV myocardium. Nontreated isolated hearts sustained severe declines of LVDP as a result of 60 (-50 +/- 8%) and 90 min (-83 +/- 7%) of ischemia, whereas diltiazem-treated hearts demonstrated only minor losses of LVDP (-17 +/- 8 and -26 +/- 2%). Diltiazem prevented losses of compliance caused by 60 or 90 min of ischemia, which were severe in nontreated hearts after the latter period of ischemia. The progressive deterioration of mechanical function observed in nontreated hearts was paralleled by depressed mitochondrial oxygen consumption and respiratory control. The respiratory activity of mitochondria isolated from cat heart mitochondria. Diltiazem also prevented significant elevations of tissue and mitochondria Ca++ content, reflecting inhibition of Ca++ influx during ischemia and reperfusion. Also, recovery of ATP levels was greater after 60 min each of ischemia and reperfusion in diltiazem-treated hearts. Thus, diltiazem exerts direct, cardioprotective effects during myocardial ischemia, presumably by inhibiting transmembrane Ca++ fluxes.
 ...
PMID:Protective effects of diltiazem during myocardial ischemia in isolated cat hearts. 726 49

Diltiazem, a calcium antagonist, was found to lessen the effect of ischemia resulting from coronary occlusion in dogs. For example, this agent preserves the high energy phosphate reservoir and decreases the inhibition of glycolytic flux at the phosphofructokinase level caused by myocardial ischemia. Diltiazem produced a marked reduction in ischemia-induced damage to the contractile elements. Increased tissue levels of lactate and free fatty acids attributable to ischemia were lowered by diltiazem. Although diltiazem increased contractility of isolated ischemia heart muscle fibers, it did not lessen the effect of ischemia on mitochondrial respiration or mitochondrial calcium binding. On the other hand, diltiazem was found to counteract the effects of ischemia followed by reperfusion on mitochondrial oxygen consumption and calcium binding.
 ...
PMID:Action of anti-anginal drugs on cardiac metabolism. 742 59

We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris. 757 50

The effects of diltiazem and phosphoramidon on sudden death induced by endothelin (ET)-1 and by big ET-1 were compared in rodents. Diltiazem (2 mg/kg, i.v.) remarkably diminished the lethal toxicity of ET-1 with a reduction in the extent of the rise in plasma immunoreactive ET-1-like activity (IR-ET-1), tissue IR-ET-1 accumulation in the heart and the rise in plasma potassium concentration. In big ET-1-induced lethality, diltiazem only slightly prolonged the latency and did not reduce the mortality. Although diltiazem moderately inhibited the rise in plasma IR-ET-1 and potassium concentration in these mice, it did not affect the accumulation of IR-ET-1 in the heart, lung or kidney. Phosphoramidon (2 mg/kg, i.v.) decreased the lethality of big ET-1 with the decrement in elevation of IR-ET-1 in the heart, lung and plasma as well as with the decrease in plasma potassium concentration, but it failed to improve any parameters in ET-1-induced lethality. In anesthetized rats, ET-1 (5 nmol/kg, i.v.) elevated ST-segment of electromyocardiograms, and diltiazem (2 mg/kg, i.v.) significantly reversed this change. Big ET-1 (25 nmol/kg, i.v.) also induced the ST-segment elevation, which was significantly inhibited by phosphoramidon but not by diltiazem. These findings suggest that accumulation of ET-1 in the heart, which may lead to lethal cardiac ischemia, is an important factor in the lethality of ET-1, while additional factors (such as hemoconcentration and bronchoconstriction) may be involved in big ET-1-induced lethality.
 ...
PMID:Possible involvement of different mechanisms in sudden death induced by endothelin-1 and big endothelin-1. 773 38

The influence of endothelin-1 on ventricular fibrillation threshold was studied in acute myocardial ischemic rats. Endothelin-1 (1.5-3.0 micrograms.kg-1 i.v.) given 5 min before ischemia reduced the ventricular fibrillation threshold in a dose- and time-dependent manner. Its effect lasted at least 60 min. A marked increase of spontaneous ventricular tachycardia and myocardial infarct size was seen and the arterial blood pressure was at a higher level (18.5-20.1/14.4-15.8 kPa) after 3.0 micrograms.kg-1. Diltiazem prevented partially from reduction of ventricular fibrillation threshold, eliminated completely the vasopressor response and limited the extension of myocardial necrosis induced by endothelin-1.
 ...
PMID:[Influence of endothelin-1 on ventricular fibrillation threshold in acute myocardial ischemic rats]. 780 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>