R. W. Baer

Pulmonary artery constriction produces a greater right ventricular dynamic afterload than lung microvascular injury in the open chest dog.

Investigators model noncardiogenic pulmonary hypertension by constricting the pulmonary artery to increase right ventricular afterload. To investigate this models validity, we compared the right ventricular afterload, quantified as pulmonary input impedance, created by constricting the pulmonary artery and by inducing a pulmonary microvascular injury (with glass beads infused into the pulmonary circulation). The pulmonary injury constriction produced a different right ventricular afterload than the microvascular injury. The constriction increased both the input resistance and the characteristic impedance. Mircrovascular injury increased only input resistance. Physiological levels of lung inflation did not influence pulmonary impedance, but lung hyperinflation increased input resistance both before and while constricting the pulmonary artery or after producing microvascular injury. Total right ventricular power output and stroke work were unchanged during each vascular intervention. Pulmonary artery constriction did not affect power output distribution, whereas microvascular injury decreased oscillatory power and its relative contribution to total power. Lung hyperinflation dramatically reduced right ventricular power and left ventricular stroke work. These effects appeared mediated by right ventricular afterload increase uncompensated for by right ventricular preload increase. These observations help explain the hemodynamic consequences of acute pulmonary hypertension and the effects of lung hyperinflation with positive end-expiratory pressure respiration in such patients.

Regulation of Transmural Myocardial Blood Flow

A major problem in understanding how myocardial blood flow is regulated is the common occurrence of subendocardial ischemia in many diseases, with or without coronary arterial disease. Two commonly held explanatory hypotheses were that high systolic intramyocardial pressures prevented flow to deep but not superficial muscle, or that in diastole tissue pressures were highest subendocardially. Neither hypothesis is tenable today, and the likeliest hypothesis is that retrograde systolic flow from the deeper muscle produces a longer time constant for diastolic flow in deep than in superficial muscle.

Effects of pressure gradients between branches of the left coronary artery on the pressure axis intercept and the shape of steady state circumflex pressure-flow relations in dogs.

When steady state pressure-flow relations are studied in the circumflex coronary artery, pressure gradients develop between it and other branches of the left coronary artery. To assess the effects of these pressure gradients, we compared the pressure axis intercept and shape of steady state circumflex pressure-flow relations in the presence and absence of gradients after autoregulation was abolished, both in the beating heart and during long diastoles in dogs. We used peripheral coronary pressures and radionuclide-labeled microspheres to assess arterial collateral flow. In the beating heart, interarterial pressure gradients reduced the curvature at low circumflex pressures, and overestimated the mean pressure axis intercept by 7.8 mm Hg (P < 0.05). The results were similar for the pressure-flow relations derived during long diastoles. This overestimation exaggerates the difference between the pressure axis intercept and coronary sinus pressure. The peripheral coronary pressure and microsphere results indicate that these effects are mediated largely by arterial collateral flow.

Arterial and venous coronary pressure-flow relations in anesthetized dogs. Evidence for a vascular waterfall in epicardial coronary veins.

The coronary circulation of anesthetized dogs was tested for the presence of vascular waterfalls by manipulating coronary arterial and coronary venous pressures. The left main coronary artery and the coronary sinus were cannulated, and relationships between coronary artery pressure, coronary sinus pressure, and coronary flow were studied. Experiments were conducted during diastolic arrests, under steady state conditions, in the absence of autoregulation. Relations of coronary flow to coronary sinus pressure at constant coronary artery pressure were consistent with the presence of a vascular waterfall in the coronary sinus. When the great cardiac vein was cannulated, relations of great vein flow to great vein pressure at constant coronary artery pressure were consistent with the presence of a vascular waterfall in the great vein, indicating that waterfall behavior can occur in epicardial veins other than the coronary sinus. In dogs on right heart bypass, with the coronary sinus and great vein uncannulated, the relationship between right atrial pressure and coronary sinus pressure showed a waterfall pattern, indicating that the waterfall is not an artifact of venous cannulation. In the right heart bypass experiments, venous waterfall behavior was seen in beating hearts as well as during diastolic arrests. We conclude that a vascular waterfall is present in epicardial coronary veins which can significantly influence coronary blood flow.

Adrenergic influence in the coronary circulation of conscious dogs during maximal vasodilation with adenosine.

The coronary arteries receive rich adrenergic innervation. The present study examines the effects of changes in adrenergic activity on the coronary circulation without the complicating influence of autoregulation. Diastolic and mean circumflex coronary artery pressure-flow relations were generated in conscious dogs and were described by their slope and zero-flow, pressure-axis intercept during vasodilation produced by intracoronary adenosine, at a dose that abolished reactive hyperemia. β-Adrenergic blockade with propranolol (1 mg/kg, iv) decreased coronary flow at all pressures, increasing diastolic pressure-axis intercept from 20.5 (4.7) (mean and SD) to 24.7 (SD 4.5) mm Hg, without a significant change in Aslope, α-Adrenergic blockade with phentolamine (0.3 μg/ kg, iv) increased flow at all pressures, with the greatest increases occurring at lower pressures. Thus, diastolic pressure-axis intercept decreased from 24.0 (SD 5.5) to 20.9 (SD 6.3) mm Hg, and calculated slope decreased slightly from 3.9 (SD 1.3) to 3.5 (SD 1.0) ml/min per mm Hg. α-Adrenergic agonist stimulation with intracoronary phenylephrine (0.3 jug/kg per min) produced little change in pressureflow relations; however, in the presence of β-adrenergic blockade, the same dose of phenylephrine decreased coronary flow at all pressures, thus increasing diastolic pressure-axis intercept from 24.4 (SD 3.7) to 29.1 (SD 3.6) mm Hg. β-Adrenergic agonist stimulation with isoproterenol (0.03 μg/kg per min, iv) produced small further increases in flow as compared with control, decreasing diastolic pressure-axis intercept from 26.0 (SD 2.9) to 24.9 (SD 2.8) mm Hg. These results suggest that significant resting α- and β-adrenergic tone can be demonstrated in coronary circulation during maximal adenosine-induced vasodilation. Resting β-adrenergic tone is near maximal, and changes in adrenergic tone exert their influence on maximal flow primarily through changes in pressure-axis intercept, rather than through changes in the slope of the pressure-flow relationship.

Instantaneous femoral artery pressure-flow relations in supine anesthetized dogs and the effect of unilateral elevation of femoral venous pressure.

Instantaneous femoral artery pressure-flow (P/Q) relations were evaluated in consecu-tive 50-msec intervals of the pulseless flow changes during cardiac arrest in six anesthetized dogs and in two anesthetized dogs with a-adrenergic blockade. In all 245 P/Q graphs obtained under conditions of normal or elevated venous pressure, either with or without a blockade, the pressure-flow relations are linear, and the zero-flow intercept on the pressure axis—reached in less than 3 seconds after the onset of cardiac arrest—is markedly higher than the simultaneous venous pressure. We believe that the zero-flow intercept is the effective downstream pressure to arterial flow and that the reciprocal of the slope of the pressure-flow line indicates the arterial resistance. The elevation of femoral venous pressure raises the effective downstream pressure and the resistance to arterial flow in the same leg. The effective downstream pressure in the contralateral leg is raised also. a-Adrenergic blockade abolishes the reflex change in the contralateral leg, but a change in P/Q relations in the manipulated leg remains. We believe that the.central reflex change could be triggered by stretch receptors in the wall of the small veins transmitted to the arterioles through a-adrenergic receptors. The encroachment on the smallest arterioles by distended small veins and by the rise in interstitial fluid pressure might be the local mechanism by which venous pressure elevation directly changes arterial P/Q relations in the manipulated leg. CircRes 47: 88-98, 1980

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease

BackgroundThe use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol.MethodsPersons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences.ResultsTwenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation.ConclusionIn persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation.

Myocardial Oxygen Transport During Leftward Shifts of the Oxygen Dissociation Curve by Carbamylation or Hypothermia

An isolated dog heart preparation was used to study the effect of left-shifting the O2 dissociation curve by carbamylation or hypothermia. The two interventions had a similar effect on the variables of O2 delivery. There were significant decreases in myocardial O2 consumption, coronary sinus PO2, and O2 extraction. There was no compensatory increase in O2 transport. Coronary flow autoregulation was somewhat blunted by hypothermia but not by carbamylation. We conclude that an increase in hemoglobin-O2 affinity is capable of limiting myocardial O2 delivery and that increases in convective O2 transport play a minor role at best in the coronary adaptation to small decreases in P50.

Subendocardial Ischemia in the Absence of Coronary Artery Disease

When people with coronary atherosclerosis develop angina pectoris or do strenuous exercise, their electrocardiograms frequently show in the left precordial leads ST segment depression that is generally ascribed to subendocardial ischemia. Similar electrocardiographic changes have been seen in patients with severe aortic stenosis or incompetence, or severe right ventricular hypertension, even when the coronary arteries are normal. In 1955 Marquis and Logan showed that patients with congenital aortic stenosis and electrocardiographic signs of subendocardial ischemia had subendocardial necrosis and fibrosis in the left ventricle, and suggested that the damage was ischemic in origin. Their findings have been confirmed many times since then (Moller, Nakeb and Edwards, 1966; Schwarz, Flameng, Schaper et al., 1978; Cheitlin, Robinowitz, McAllister et al., 1980).

The Influence of Hypoxic Hypoxia on Coronary Blood Flow Heterogeneity

The delivery of oxygen and other nutrients to myocardial tissue is a two-step process involving first, convective delivery to the microcirculation and then, diffusive delivery across the capillary wall and interstitium into the tissue cells. The diffusive part of this process is important for substances like oxygen which are normally highly extracted. The amount of oxygen extracted is a function of capillary transit time (Honig et al., 1992). Capillary transit time, in turn, is directly related to capillary flow and inversely related to capillary path length. Heterogeneities in capillary transit time lead to heterogeneities in the extraction process. There is direct evidence that coronary blood flow shows heterogeneity (Marcus et al., 1977; King et al., 1985) and indirect evidence for heterogeneity of capillary transit times (Rose and Goresky, 1976; Rose et al., 1980). This can cause diffusion heterogeneity for a substance like oxygen which exhibits partially flow-limited diffusion.