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

Diltiazem retards ischemic arrhythmias and reduces cellular depolarization, as inferred from recordings of T-Q segment depression (delta T-Q). To explore this further, we correlated delta T-Q with the extracellular K+ electrode potential (delta EK) during serial ischemic trials. delta T-Q and delta EK were uniform in control trials, but decreased markedly in trials that immediately followed diltiazem infusion (0.5 mg/kg). delta EK at 2 min of ischemia was reduced from 11.8 +/- 1.3 to 7.4 +/- 1.2 mV; while delta T-Q was reduced from 7.2 +/- 0.5 to 4.4 +/- 0.7 mV. The effect of diltiazem on ischemic depolarization is largely, but not entirely explained by reduction of delta EK.
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PMID:Effect of diltiazem on ischemic myocardial depolarization and extracellular K+ accumulation. 375 82

The effective refractory period (ERP) during the period of the alternation of the ST-T complex (STTA) in the ischemic myocardium was determined using a synchronized system of electrical stimulators and a bipolar epicardial electrode during acute coronary occlusion in anesthetized dogs. Epicardial unipolar electrograms (UP), epicardial bipolar electrograms (BP) and monophasic action potentials (MAP) were also recorded from ischemic areas. ERP in ischemic areas was prolonged, as ischemia progressed, and during the period of STTA ERP also alternately changed. A lower or negative deflection of the ST-T complex was accompanied by a longer ERP, and a higher or monophasic ST-T complex was accompanied by a shorter ERP. A good correlation was observed between the degrees of alternation in ERP and of STTA. MAP also showed an alternation in its duration and its amplitude. The alternation in duration preceded the alternation in amplitude. A lower or negative deflection of the ST-T complex corresponded to a MAP with a longer duration and a larger amplitude. During the period of STTA, a long conduction delay followed the negative deflection of the ST-T complex. A marked conduction delay appeared only during a period of STTA. Diltiazem and nifedipine inhibited STTA and an alternation in ERP. In conclusion, STTA is associated with an alternation in ERP and in conduction delay, and calcium antagonists attenuate both STTA and an alternation in ERP.
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PMID:Alternation in refractoriness and in conduction delay in the ischemic myocardium associated with the alternation in the ST-T complex during acute coronary occlusion in anesthetized dogs. 380 58

To determine the therapeutic effect of two vasodilators, adenosine and diltiazem, in mesenteric ischemia, 13 dogs were treated with an intra-arterial perfusion of the drugs after digitalis intoxication. Blood flow was restored to the control value after a dose of 2 micrograms/kg/minute adenosine or 5 micrograms/kg/minute diltiazem. The advantage of adenosine is that its effect begins and ends very rapidly, but because doses of more than 2 micrograms/kg/minute may cause a drop in blood pressure, strict pressure control is mandatory when the drug is applied clinically. Its limited use is appropriate, for example, when operative measures cannot be excluded. Diltiazem can be used for long-term therapy with a reduced risk of a drop in blood pressure.
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PMID:Adenosine and diltiazem. A new therapeutic concept in the treatment of intestinal ischemia. 398 68

The calcium antagonist, diltiazem, was evaluated for its ability to reduce the extent of myocardial injury resulting from 90 min of left circumflex (LCX) coronary artery occlusion in anesthetized dogs. Administration of diltiazem (0.75 mg/kg over 10 min, followed by 600 microgram/kg/h for 4 h) was initiated 30 min prior to LCX occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres 30 min after LCX occlusion, and at 45 min and 24 h after reperfusion. At 24 h, after obtaining hemodynamic and RMBF measurements, excised hearts were processed by perfusion staining to determine the percent of left ventricle (LV) perfused by LCX (area at risk) and infarct size, with triphenyltetrazolium chloride. Infarct size, expressed as a percentage of the area at risk, was significantly lower in the diltiazem-treated group compared to the control group (27 +/- 4 vs. 42 +/- 5%, respectively). The area at risk, expressed as a percentage of left ventricular mass, was similar in both groups [41 +/- 2 and 44 +/- 3% (area at risk-LV)]. In addition, the marked elevation of tissue Ca2+ content in noninfarcted and infarcted myocardium within the area at risk (18 +/- 2 and 42 +/- 8 mumol Ca2+/g) in control animals was attenuated by diltiazem (6 +/- 3 and 18 +/- 8 mumol Ca2+/g). Diltiazem did not increase blood flow to ischemic myocardium during LCX occlusion. However, reflow to the inner layers of formerly ischemic myocardium during reperfusion was significantly greater in diltiazem-treated dogs. Both arterial blood pressure and heart rate were significantly lower in the diltiazem -treated group. In addition, mortality (1 vs. 4) and occurrence of ventricular arrhythmias during reperfusion were lower in diltiazem-treated dogs. The data suggest that diltiazem reduces myocardial ischemic injury by lowering myocardial oxygen demands indirectly via favorable hemodynamic alterations, and directly by limiting transmembrane Ca2+ fluxes during ischemia and reperfusion.
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PMID:Effect of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs. 617 13

Ischemia was induced by lowering the afterload pressure of the perfused working rat heart, and continued until the heart was reperfused by raising the after load. After ischemia, the following changes were observed: decreases in the pressure-rate product (peak aortic pressure X heart rate) and coronary flow; depletion of adenosine triphosphate and creating phosphate; and accumulation of lactate. When the heart was exposed to ischemia for more than 20 min, reperfusion of the ischemic heart could not restore the pressure-rate product and the tissue adenosine triphosphate completely, suggesting that irreversible ischemic damage occurred. Diltiazem (2.41 X 10(-6), 1.21 X 10(-5), and 2.41 X 10(-5) M) or propranolol (1.69 X 10(-5) and 3.38 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. In the presence of diltiazem or propranolol, the levels of adenosine triphosphate and creatine phosphate were preserved even after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia with the buffer containing diltiazem or propranolol recovered the pressure-rate product that had been decreased by ischemia, depending on the concentration of diltiazem or propranolol provided. These results indicate that diltiazem, as well as propranolol, delays the onset of irreversible ischemic damage of the heart, suggesting their protective effects on the ischemic myocardium.
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PMID:Effects of diltiazem and propranolol on irreversibility of ischemic cardiac function and metabolism in the isolated perfused rat heart. 619 60

Calcium channel blockade appears to be at least as effective as beta-blockade in the treatment of anginal syndromes, but whether a similar protective effect is afforded against sudden death is unknown. In order to compare experimental antifibrillatory effects of calcium channel blockade (diltiazem), beta-adrenoceptor blockade (timolol), and nitroglycerin, we measured ventricular fibrillation (VF) thresholds in anesthetized, open-chest dogs before and after 3 min of coronary ischemia before and after i.v. administration of each of these drugs or saline. In control studies, VF occurred after delivery of 11.8 +/- 5.3 mA (X +/- SD) in the nonischemic state and 9.4 +/- 4.6 mA during ischemia (n = 25). During saline administration, no significant change in VF threshold occurred during ischemia, and a minimal increase over time occurred in the nonischemic state. Diltiazem (0.04-0.08 mg/kg/min; n = 10) increased VF thresholds under both ischemic (by 7.7 mA, p less than .01) and nonischemic (by 5.5-5.8 mA, p less than .05) conditions. Timolol (0.03 mg/kg; n = 8) caused substantially greater increases in VFT during nonischemia and ischemia: 11.2 +/- 2.8 mA to 51.6 +/- 38.5 mA (nonischemia) and 8.4 +/- 3.8 mA to 28.7 +/- 16.4 mA (ischemia), both p less than 0.02. VF thresholds were not changed after nitroglycerin (n = 8). Differing experimental effects of these drugs emphasize the need for clinical studies to establish the relative potential of calcium channel blockade and nitroglycerin to reduce mortality in ischemic heart disease.
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PMID:Experimental antifibrillatory effects of calcium channel blockade with diltiazem: comparison with beta-blockade and nitroglycerin. 620 80

The three major calcium channel blocking agents, diltiazem, nifedipine and verapamil, inhibit calcium entry into excitable cells. Despite this apparent common action at the cell membrane, these drugs produce quantitative and frequently qualitative differences in cardiovascular variables (for example, heart rate, atrioventricular [A-V] conduction and myocardial inotropic state) when evaluated at equieffective vasodilator doses. All three drugs increase coronary blood flow in a dose-dependent fashion (nifedipine greater than diltiazem = verapamil), and produce a negative inotropic effect in vitro in isolated atria and ventricles, also in a dose-dependent manner (verapamil greater than nifedipine greater than diltiazem). However, in conscious dogs nifedipine increases, verapamil decreases and diltiazem has little effect on the inotropic state. A-V conduction is slowed by diltiazem and verapamil but not by nifedipine in anesthetized dogs and in conscious dogs as judged from the P-R interval in the electrocardiogram. Heart rate is slowed in pentobarbital-anesthetized animals but is accelerated in conscious dogs (nifedipine greater than verapamil greater than diltiazem). Nifedipine also appears to interfere significantly with the arterial baroreceptor reflex by an apparent vagolytic action that is less evident with diltiazem and verapamil. Diltiazem, and possibly verapamil and nifedipine as well, appears to retard myocardial damage that accompanies ischemia. The mechanisms and sites of action of these drugs are presumed to be at the cell membrane; however, intracellular sites may also be involved.
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PMID:Differential cardiovascular effects of calcium channel blocking agents: potential mechanisms. 627 75

Diltiazem, nifedipine, and verapamil inhibit calcium entry into cells via different mechanisms with different pharmacologies. They display different relative effects on different cardiovascular functions, a complex interplay of direct actions and adrenergic reflexes. Peripheral arterial vasorelaxation causes adrenergic reflex activity which opposes their direct negative chronotropic, dromotropic, inotropic, and hypotensive actions. Verapamil's most potent activity is electrophysiologic, and nifedipine's effects are hemodynamic; diltiazem acts like a less-potent combination of verapamil and nifedipine. All three drugs are efficacious in angina. These three drugs may not be interchangeable in all patients, but individualization of therapy is possible. Future indications for calcium channel blocker therapy may include hypertrophic cardiomyopathy, cerebral vasospasm, migraine headaches, pulmonary hypertension, asthma, esophageal spasm, intestinal ischemia, Raynaud's phenomenon, dysmenorrhea, and premature labor.
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PMID:Calcium channel blockers in emergency medicine. 638 Mar 52

Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effect on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic "injury" potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15-25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 +/- 2.7 mV before diltiazem and 6.1 +/- 1.6 mV afterward (P less than 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P less than 10(-5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocclusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.
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PMID:Reduction of ischemic depolarization by the calcium channel blocker diltiazem. Correlation with improvement of ventricular conduction and early arrhythmias in the dog. 669 97

The effect of diltiazem on the development of infarcts was investigated in porcine hearts. The left anterior descending coronary artery was occluded in each of 32 anesthetized pigs for 75 min and was reperfused for 4 hr. Diltiazem (15 micrograms/kg X min) was infused in 11 pigs for 30 min before occlusion (therapy A) and in another eight pigs before reperfusion (therapy B). Eleven pigs served as controls. Tissue concentrations of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) were determined in transmural needle biopsy samples taken from the ischemic apex after 70 min of ischemia. The infarct size, expressed as the ratio of the infarcted tissue over the area at risk of necrosis multiplied by 100, amounted to 79 +/- 20% in the control group. Although there was no significant difference between hemodynamics in the control and the treated groups, pretreatment with diltiazem significantly reduced infarct size (53 +/- 26%; p = .025). Reduction of infarct size by therapy B did not reach the required level of significance (66 +/- 33%). The ischemic loss of ATP and NAD was significantly lower in the pretreated group, which further indicates that the beneficial effect of diltiazem was exerted primarily during ischemia and not during reperfusion.
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PMID:The effect of two different diltiazem treatments on infarct size in ischemic, reperfused porcine hearts. 670 55


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