title: Nitric oxide-dependent vasodilation maintains blood flow in true hibernating myocardium.
abstract: Patients with chronic coronary artery disease may exhibit chronically depressed regional myocardial function, which can be reversed by revascularization. This was called hibernating myocardium, since it was thought that myocardial blood flow was also chronically reduced and since animals during true hibernation are thought to have downregulated function and blood flow. The missing link in this syllogism, whose discovery became our goal, was to measure myocardial blood flow during true hibernation. Five woodchucks (Marmota monax) were anesthetized and chronically instrumented. Hemodynamics were recorded prior to placement in a hibernaculum and again after the animals displayed a stable period of hibernation. Body temperature had fallen from 35.7 +/- 0.5 to 13.4 +/- 0.6 degrees C. Heart rate, mean aortic pressure, and left ventricular dP/dt had decreased, P < 0.05, by 67 +/- 12% from 86 +/- 4 bpm, 36 +/- 11% from 76 +/- 4 mmHg, and 61 +/- 11% from 1924 +/- 222 mmHg/s, respectively. Although renal blood flow, as assessed by radioactive microspheres, had decreased by 95 +/- 2% and overall cardiac output fell by approximately 84%, surprisingly, transmural myocardial blood flow did not fall during hibernation (0.70 +/- 0.16 ml/min/g) relative to when awake (0.84 +/- 0.09 ml/min/g). Interestingly, during hibernation, nitric oxide (NO) synthase inhibition resulted in a significant decrease, P < 0.05, in myocardial blood flow (-41 +/- 5%) and increase in coronary vascular resistance (CVR, +90 +/- 17% from 77 +/- 13 mmHg min g/ml). Thus, true mammalian hibernation results in downregulation of blood flow to the visceral organs, e.g. to the kidneys, but a surprising maintenance of myocardial blood flow, which appears to be due to an NO mechanism.
authors.affiliation: Tufts University, School of Veterinary Medicine, North Grafton, MA 01536, USA.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Kudej
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D001835:Body Weight; D003326:Coronary Circulation; D005260:Female; D006339:Heart Rate; D006605:Hibernation; D008297:Male; D008392:Marmota; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow; D013152:Splanchnic Circulation; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide