TY - JOUR
T1 - Effects of diltiazem, a calcium channel inhibitor, in retarding cellular damage produced during early myocardial ischemia in pigs
T2 - A morphometric and ultrastructural analysis
AU - Fujiwara, Hisayoshi
AU - Ashraf, Muhammad
AU - Millard, Ronald W.
AU - Sato, Shigeru
AU - Schwartz, Arnold
N1 - Funding Information:
From the Departments of Pathology and Laboratory Medicine. Pharmacology and Cell Biophysics. and Internal Medicine (Division of Cardiology), University of Cincinnati Medical Center, Cincinnati. Ohio. This work was supported in part by grants from the Southwestern Ohio Chapter of the American Heart Association (R.W.M.); Grants HL23558 (R.W.M), HL23597 (M.A.) and POI H22619 (A.S., Core I) from the National Institutes of Health, Bethesda, Maryland. Dr. Ashraf is the recipient of Research Career Development Award K04HLOO540. Manuscript received May 18, 1983; revised manuscript received December 19, 1983, accepted December 21, 1983.
PY - 1984
Y1 - 1984
N2 - A protective effect of intravenous diltiazem pretreatment on transmural histologic damage in ischemic hearts of 30 pigs was determined morphometrically. The pig hearts were rendered ischemic by ligation of the distal left anterior descending coronary artery for 20, 40 and 120 minutes in separate experiments. Heart rate, left ventricular systolic pressure and systemic diastolic pressure decreased slightly during 40 minutes of occlusion, and then recovered to control levels. However, there were no significant differences between control and diltiazem-treated groups. Blood flow, measured by the microsphere technique, was uniformly absent in the ischemic areas in both control and diltiazem-treated hearts. In the few cell layers immediately beneath the endocardium and epicardium, little cellular damage was observed in either group regardless of the duration of ischemia. In the subendocardial, mid-myocardial and subepicardial layers, less cellular damage was detected after all periods of ischemia in hearts exposed to diltiazem in comparison with that observed in control hearts. However, even in the drug-treated hearts, after 2 hours of occlusion, the cells remained severely injured. The protective effect of diltiazem on the cellular integrity in the ischemic myocardial regions appears to be independent of blood flow and may be a reflection of a direct effect of diltiazem on myocytes. The precise mechanism is unresolved. Nevertheless, in the ischemic heart without a significant collateral circulation, pretreatment with the calcium channel blocking drug, diltiazem, results in a delayed onset of cellular damage after acute coronary artery ligation and less cellular damage at ischemic periods up to 40 minutes' duration.
AB - A protective effect of intravenous diltiazem pretreatment on transmural histologic damage in ischemic hearts of 30 pigs was determined morphometrically. The pig hearts were rendered ischemic by ligation of the distal left anterior descending coronary artery for 20, 40 and 120 minutes in separate experiments. Heart rate, left ventricular systolic pressure and systemic diastolic pressure decreased slightly during 40 minutes of occlusion, and then recovered to control levels. However, there were no significant differences between control and diltiazem-treated groups. Blood flow, measured by the microsphere technique, was uniformly absent in the ischemic areas in both control and diltiazem-treated hearts. In the few cell layers immediately beneath the endocardium and epicardium, little cellular damage was observed in either group regardless of the duration of ischemia. In the subendocardial, mid-myocardial and subepicardial layers, less cellular damage was detected after all periods of ischemia in hearts exposed to diltiazem in comparison with that observed in control hearts. However, even in the drug-treated hearts, after 2 hours of occlusion, the cells remained severely injured. The protective effect of diltiazem on the cellular integrity in the ischemic myocardial regions appears to be independent of blood flow and may be a reflection of a direct effect of diltiazem on myocytes. The precise mechanism is unresolved. Nevertheless, in the ischemic heart without a significant collateral circulation, pretreatment with the calcium channel blocking drug, diltiazem, results in a delayed onset of cellular damage after acute coronary artery ligation and less cellular damage at ischemic periods up to 40 minutes' duration.
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U2 - 10.1016/S0735-1097(84)80281-8
DO - 10.1016/S0735-1097(84)80281-8
M3 - Article
C2 - 6715703
AN - SCOPUS:0021237480
SN - 0735-1097
VL - 3
SP - 1427
EP - 1437
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -