Effect of hypertension and hypertension-glucose intolerance on myocardial ischemic injury.
Systemic hypertension and type 2 diabetes mellitus are major risk factors for myocardial infarction. Yet, glucose intolerance, a prelude stage to type 2 diabetes, is associated with reduced infarct size. Since chronic hypertension adversely affects the myocardium, we tested the hypothesis that the coexistence of systemic hypertension and glucose intolerance reverses the cardioprotection associated with impaired glucose tolerance. Hearts from 9-month-old animals were subjected to a 40-minute occlusion of the left coronary artery followed by 2 hours of reperfusion. Before ischemia, similar values for the four experimental groups were observed for the coronary flow, heart rate, and maximum ventricular pressure. During the course of the ischemia-reperfusion insult, the two hypertensive groups displayed greater reductions in contractility than their normotensive counterparts. Infarct size was lower in the normotensive glucose-intolerant rat than in the normotensive control rat. Surprisingly, the hypertrophied hearts of the hypertensive and hypertensive glucose-intolerant rats displayed reduced infarct size (P<0.05). However, raising the afterload pressure from 100 to 160 cm H2O increased infarct size in the two hypertensive groups. This narrowed the differential between the hypertensive glucose-intolerant (160 cm H2O) and the normotensive control (100 cm H2O) rats. Nonetheless, at the higher afterload pressure, infarct size was less in the hypertensive glucose-intolerant rats than in their hypertensive counterparts. In conclusion, the impairment in contractile function despite the reduction in infarct size underscores the increased susceptibility of the hypertrophied, hypertensive heart to ischemic injury. Furthermore, exacerbation of cell death at elevated afterload pressure indicates the potential benefit of aggressive antihypertensive therapy.
Mozaffari
Mahmood S
MS
Department of Oral Biology and Maxillofacial Pathology, Medical College of Georgia School of Dentistry, Augusta, Ga 30912-1128, USA. Mmozaffa@mail.mcg.edu
Schaffer
Stephen W
SW
D000818:Animals; D018149:Glucose Intolerance / Q000150:complications*; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000209:etiology; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D009924:Organ Culture Techniques; D051381:Rats; D011921:Rats, Inbred WKY