Neuropeptide-Y. A peptide found in human coronary arteries constricts primarily small coronary arteries to produce myocardial ischemia in dogs.

Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.

Contrasting effects of verapamil and nifedipine on pH of ischemic myocardium in the dog.

It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive measurement of conjunctival PCO2 with a fiberoptic sensor.

A miniaturized fiberoptic PCO2 probe permits direct measurement of tissue PCO2 on nonkeratinized tissue surfaces without the heating effects produced by transcutaneous PCO2 sensors. This study of anesthetized dogs compared PCO2 measured at the palpebral conjunctiva (PcjCO2) with PaCO2 and mixed venous (PVCO2) measurements during normovolemic normotension and hypovolemic hypotension. During the control period, the average PcjCO2 was 3 +/- 1 (SEM) torr greater than PaCO2 (r = 0.98) when the latter ranged from 20 to 80 torr. There was a close association (r = 0.94) between PcjCO2 and PaCO2 when the cardiac index (CI) was greater than 2.0 L/min X m2. However, as CI decreased below this value, PcjCO2 and PaCO2 were less well correlated (r = 0.69). PcjCO2 was closely associated with PVCO2 at all stages of the experiment, both above (r = 0.95) and below (r = 0.82) a CI of 2 L/min X m2. Fiberoptic conjunctival PCO2 monitoring seems promising as a noninvasive measure of physiologic status.

Continuous monitoring of tissue pH with a fiberoptic conjunctival sensor.

To assess the relationship between conjunctival pH (pHcj), arterial pH (pHa), and cardiorespiratory variables during normal and low-flow conditions, hemorrhagic hypotension was induced in eight dogs. Conjunctival pH became significantly less than control values after a hemorrhage volume of 15 mL/kg (P less than .05); mean arterial pressure (MAP) did not fall until blood loss was 20 mL/kg. There was poor correlation between pHcj and pHa, cardiac index (CI), or MAP. There was a high degree of correlation, however, between pHcj-pHa difference (delta pH) and MAP (r = -0.886), CI (r = -0.846), and tissue oxygen extraction ratio (r = .896). The results of these experiments indicate that pHcj is a sensitive monitor of peripheral tissue perfusion, and that the degree of physiologic compromise associated with hemorrhage can be determined by analysis of the difference between arterial and conjunctival pH.

Effect of verapamil on pH of ischemic canine myocardium.

Verapamil has been shown to depress the contractility of ischemic myocardium. The present study was designed to determine whether that effect is due to an increase in ischemic injury caused by the drug or whether it might reflect a protective effect. A critical partial occlusion was effected on the left anterior descending coronary artery of 16 open chest foxhounds. A fiberoptic pH probe was implanted in the subendocardium of the ischemic zone, and coronary blood flow was reduced by 79% from a control value of 38 +/- 4 ml/min and held constant. Mean coronary perfusion pressure was decreased 48% from its control value of 90 +/- 6 mm Hg and remained constant. Eight animals were treated with intravenous verapamil, beginning 20 to 30 minutes after the onset of ischemia, in incremental doses (5, 10 and 20 micrograms/kg per min) and eight were treated with placebo. The pH of the ischemic zone increased after institution of treatment in the verapamil group (+ 0.04 +/- 0.05 pH unit) whereas it decreased in the placebo group (- 0.06 +/- 0.4 pH unit) during the first dose (p less than 0.05). Although the difference in pH between the two groups was marked at all doses (p less than 0.03) compared with control partial occlusion, verapamil caused no significant change in heart rate (+ 0.1 +/- 1 beat/min in the verapamil group versus + 0.6 +/- 4.5 beats/min in the placebo group), mean arterial pressure (- 7.5 +/- 4 versus - 4.3 +/- 3 mm Hg, respectively) or cardiac output (- 0.2 +/- 0.07 versus - 0.02 +/- 0.04 liters/min, respectively) comparing control with the first or the second dose of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmural pH gradient in canine myocardial ischemia.

The subendocardium is more susceptible to ischemia than the subepicardium. Studies during critical coronary stenosis have demonstrated subendocardial hypoperfusion relative to the subepicardium and transmural gradients in certain tissue metabolites. Although ischemia causes acidosis, the existence of a transmural pH gradient has never been demonstrated or quantitated. Thus we reduced coronary blood flow to 20 +/- 5% of normal in eight open chest anesthetized (morphine sulfate and pentobarbital) dogs and to 45 +/- 5% in two dogs. We implanted specially designed miniature fiber-optic pH probes in normal and ischemic subendocardium (depth 5.5-8 mm) and subepicardium (depth 3-4 mm). Separate experiments validated use of the fiber-optic pH probe system to measure tissue pH. Although both probes were located in the ischemic zone, there was a large transmural gradient, i.e., from normal pH values (7.36) in the subepicardium to severely acidotic (pH 6.94) 2 mm deeper in the subendocardium. This marked difference in pH between nearby transmural layers may have important implications regarding arrhythmogenesis in the setting of acute myocardial ischemia.

Force relaxation and permanent deformation of erythrocyte membrane.

Force relaxation and permanent deformation processes in erythrocyte membrane were investigated with two techniques: micropipette aspiration of a portion of a flaccid cell, and extension of a whole cell between two micropipettes. In both experiments, at surface extension ratios less than 3:1, the extent of residual membrane deformation is negligible when the time of extension is less than several minutes. However, extensions maintained longer result in significant force relaxation and permanent deformation. The magnitude of the permanent deformation is proportional to the total time period of extension and the level of the applied force. Based on these observations, a nonlinear constitutive relation for surface deformation is postulated that serially couples a hyperelastic membrane component to a linear viscous process. In contrast with the viscous dissipation of energy as heat that occurs in rapid extension of a viscoelastic solid, or in plastic flow of a material above yield, the viscous process in this case represents dissipation produced by permanent molecular reorganization through relaxation of structural membrane components. Data from these experiments determine a characteristic time constant for force relaxation, tau, which is the ratio of a surface viscosity, eta to the elastic shear modulus, mu. Because it was found that the concentration of albumin in the cell suspension strongly mediates the rate of force relaxation, values for tau of 10.1, 40.0, 62.8, and 120.7 min are measured at albumin concentrations of 0.0, 0.01, 0.1, and 1.% by weight in grams, respectively. The surface viscosity, eta, is calculated from the product of tau and mu. For albumin concentrations of 0.0, 0.01, 0.1, and 1% by weight in grams, eta is equal to 3.6, 14.8, 25.6, and 51.9 dyn s/cm, respectively.

Parameters of stimulation and perception in an artificial sensory feedback system.

The relationships between stimulus parameters and perceptions in a prosthetic feedback system were measured using psychophysical methods. Electrical stimulation of the median nerve produced a monotonic relation between frequency of stimulation and the perceived magnitude of the stimulus. There were two qualitatively different perceptions of the stimulation; one for low frequencies and one for high. These two qualities fit different psychophysical continuua, kind of stimulation, and amount of stimulation.