Inhibition of peripheral vascular compensation after the induction of myocardial ischemia in dogs.

Abstract

The fact that peripheral vascular resistance fails to increase, or does so to only a small degree, thus contributing to hypotension after the onset of myocardial ischemia, has been noted in both clinical and experimental studies. We examined this phenomenon in canine kidney, mesentery, spleen, and skeletal muscle after occlusion via ligation of the circumflex coronary artery. Animals anesthetized with pentobarbital sodium (30 mg/kg, IV) and with intact vagus nerves exhibited reduced cardiac output (CO), maintenance of mean arterial blood pressure (MAP) at or near control levels, and increased total peripheral resistance (TPR). Blood flows to the kidney (RBF) and mesentery (MBF) were decreased resulting in substantial elevations of renal vascular resistance (RVR) and mesenteric vascular resistance (MVR). Blood flow supplied to the hindlimb skeletal muscle (FBF) by the femoral artery did not vary substantially from control levels and, therefore, neither did femoral vascular resistance (FVR). Splenic arterial blood flow (SpBF) was somewhat decreased but splenic vascular resistance (Sp VR) remained un changed. Heart rate exhibited no change from control levels. When coronary artery ligation was preceded by bilateral cervical vagot omy, CO was decreased as before but MAP exhibited sustained decreases. No change from control values was noted in RBF, FBF, MBF, or SpBF. RVR, MVR, and Sp VR were significantly decreased while FVR remained unchanged. TPR in all cases was increased but not to the same degree as was noted in nonvagotomized animals. Again, no change in heart rate occurred. Unlike the hemodynamic pattern observed in vagotomized dogs subjectedto the induction of myocardial ischemia, treatment of animals with a cholinergic blocking dose of atropine sulfate (1 mg/kg, IV) before coronary artery occlusion produced maintenance of MAP at or near control levels, lesser and slower reductions of CO and significantly increased TPR. No change was observed in RBF, FBF, MBF, SpBF or in RVR, FVR, MVR, and SpVR. Although there were no changes in heart rate from control levels, these values in atropinized dogs were usually higher than corresponding figures in other series. When the induction of mild pericardial tamponade was substituted for coronary artery ligation, both vagotomized and non-vagotomized dogs exhibited normal peripheral compensations to the resulting hypotension and CO reduction, i.e., RBF decreased markedly and RVR was substantially increased as was TPR. No change in heart rate occurred. These results indicate that (1) myocardial ischemia is necessary to trigger the abnormal loss of peripheral vascular compensatory responses; (2) vagal afferent nerves serve a protective function by mediating normal compensatory maneuvers, and (3) an additional mechanism, activated by ischemia but masked by the vagi, may cause inappropriate vasodilation when vagal afferent nerve activity is lost. A model has been constructed that presents a possible mechanism mediating the described phenomena.