Laboratory Investigation Hypertension

These studies were performed to test the hypothesis that left ventricular hypertrophy arising as a complication of chronic hypertension is associated with impaired coronary autoregulation. Twelve dogs with hypertension and left ventricular hypertrophy (one-kidney, one-clip model) and 11 normal dogs were instrumented and subsequently studied while conscious. Circumflex pressure, measured with an intracoronary catheter, was adjusted to 100, 75, and 40 mm Hg with a hydraulic occluder that was placed proximally. At each circumflex pressure, myocardial perfusion was measured with radioactive microspheres. Reduction of circumflex pressure over this range did not significantly alter heart rate, left atrial pressure, or arterial pressure. In normal dogs, reduction of circumflex pressure did not alter total myocardial pefusion or the transmural distribution of perfusion. In contrast, in dogs with hypertension and left ventricular hypertrophy, circumflex subendocardial perfusion decreased 46% when pressure was decreased from 100 to 40 mm Hg (p < .05 compared with normal). Autoregulation was quantified for each third of myocardium with the use of autoregulatory gain values (1 = perfect autoregulation; 0 = the absence of autoregulation). For pressure changes of 100 to 75 mm Hg, values for autoregulatory gain were near unity for all layers of myocardium in both groups of animals. When pressure was decreased from 75 to 40 mm Hg, values for autoregulatory gain among the normal and hypertensive groups were, respectively: for subepicardium 1 0.2 (mean + SE) vs 0.9 0.2 (p = NS), for the midwall 0.8 + 0.2 vs 0.5 ± 0.2 (p = NS), and for the subendocardium 0.8 0.1 vs 0.1 + 0.2 (p < .05). We conclude that hypertension and left ventricular hypertrophy are associated with a profound impairment of the lower range of autoregulation in the subendocardial myocardium. This abnormality of local control of myocardial perfusion may predispose the hypertrophied myocardium to ischemia or infarction in the setting of either coronary stenoses or systemic hypotension. Circulation 77, No. 5, 1108-1115, 1988. AUTOREGULATION is defined as the propensity for blood flow to an organ to be maintained at a constant level over a wide range of perfusion pressures.1' 2 In the coronary circulation of anesthetized animals, myocardial perfusion remains reasonably constant between pressures of 40 and 150 mm Hg.]6 Below this range of pressures (the autoregulatory range), myocardial perfusion decreases in a linear fashion.3 6 Above this range myocardial perfusion progressively increases as coronary perfusion pressure is increased.6 7 This autoregulatory range is substantially narrower in the subFrom the Cardiovascular Center and VA Medical Center, University of Iowa, Iowa City. Supported by NIH grants HL 32717, HL 201046, Ischemic SCOR HL 32295, and a Merit Review Grant from the Veterans Administration. Dr. Harrison is a recipient of the Established Investigator Award of the American Heart Association. Address for correspondence: David G. Harrison, M.D., E 317A General Hospital, University of Iowa, Iowa City, IA 52242. Received Sept. 15, 1987; revision accepted Jan. 28, 1988. endocardium than in the subepicardium.7 The factors responsible for coronary autoregulation are unknown but likely include both metabolic and myogenic influences.' In the cerebral circulation, chronic hypertension results in a shift of both the lower and upper limits of autoregulation.8-10 Although the effect of hypertension and concomitant left ventricular hypertrophy on coronary autoregulation have not been examined previously, there are several reasons to suspect that coronary autoregulation may be altered by this condition, especially the response to lowering perfusion pressure. First, almost all manifestations of coronary artery disease are exaggerated in patients with hypertension and left ventricular hypertrophy. It is conceivable that alterations of coronary autoregulation may contribute to the poor outcome in these patients. Second, hypertrophy of either ventricle is associated with blunted coronary CIRCULATION 1108 by gest on A ril 7, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-HYPERTENSION vasodilatation in response to either transient ischemia or pharmacologic stimuli.11-15 Thus, one might assume that autoregulatory vasodilatation in response to decreased perfusion pressure may also be abnormal in hypertension and left ventricular hypertrophy. This assumption may not be true because it has recently been found that vasodilator reserve to pharmacologic stimuli persists when coronary perfusion is reduced by a decrease in the perfusion pressure below the autoregulatory range.16-19 Several technical limitations have made it difficult to study the effect of hypertension and left ventricular hypertrophy on coronary autoregulation. First, coronary autoregulation is difficult to demonstrate consistently in the anesthetized, open-chest animal. Even under optimal conditions, autoregulatory gain values (when 1 is perfect autoregulation and 0 is absence of autoregulation20) are often less than 0.7 in these preparations. Second, in conscious animals, when a coronary artery is constricted to reduce perfusion pressure, it is difficult to measure intracoronary perfusion pressure distal to the stenosis. Finally, abnormalities of coronary autoregulation may result in regional rather than global alterations in myocardial perfusion. Thus, measurements of flow through epicardial coronary arteries with either electromagnetic or Doppler techniques may be insensitive to changes in autoregulation in myocardial hypertrophy. In the present study we sought to determine the effect of chronic hypertension and left ventricular hypertrophy on the lower limit of autoregulation. We studied conscious, previously instrumented dogs 3 to 6 months after the onset of renal hypertension. Regional myocardial perfusion was assessed distal to an imposed coronary stenosis sufficient to decrease coronary pressure to desired levels. Our findings suggest that hypertension and left ventricular hypertrophy are associated with an impairment of the lower limit of coronary autoregulation in the subendocardial myocardium.