Discriminant analysis of transmission of elevated blood pressure in first generation offspring of African green monkeys.

A linear discriminant analysis was applied to blood pressure data of 162 first generation colony-born offspring of normotensive (C), hypertensive (H), or borderline hypertensive (B) African green monkeys who were being selectively bred in an attempt to establish a strain of spontaneously hypertensive monkeys. The offspring were classified according to their parents' blood pressures as CC, HH, or Mixed (e.g. HC). Blood pressures were measured by indirect methods from unanesthetized offspring aged 0.5-6 years of age. The discriminant score was used to classify each of the 533 blood pressure measurements of the CC, Mixed, and HH offspring into one of three predicted groups: normotensive, borderline hypertensive, or hypertensive. The group means of the three predicted groups compared without regard to offspring type were significantly different (p less than .001). In addition, the percentage of blood pressure measurements predicted to be normal or elevated differed among the three offspring groups (p less than .001). 82% of the blood pressure measurements from CC offspring were classified as normotensive, compared with 58% and 40% of the blood pressure measurements from the Mixed and HH groups, respectively. In contrast, 25% of the blood pressure measurements from the HH groups were classified as hypertensive, compared with 10% and 4% from the Mixed and CC groups, respectively. Blood pressures of the normotensive, borderline hypertensive, and hypertensive subgroups derived from the CC group were consistently and significantly lower (p less than .001) than their respective counterparts in the Mixed and HH groups. The results of the discriminant analysis indicate a trimodal distribution of blood pressures in the first generation offspring and a significant separation of blood pressures among the offspring after a single generation.

Electrocardiographic effects of experimental myocardial infarction in pigs.

Myocardial infarctions were produced in young domestic farm pigs by ligating coronary arteries. Arteries ligated in four groups were (A) left anterior descending, (B) branches of left anterior descending, (C) left circumflex, and (D) right coronary artery. After 7 or 8 days, the hearts were removed and dissected and the infarcted areas measured. Vectorcardiograms were taken before ligation and just before termination. High recording speeds and sensitivities were used so that details of the QRS complexes could be seen. Difference vectors were computed as a function of time during QRS. In groups A and B, statistically significant differences in QRS components before and after ligation were found. Also, there were statistically significant correlations between vectorcardiographic deflections and the ratio of infarct weight to heart weight. The changes were related to known excitation patterns of the pig heart.

Development of a nonhuman primate model for spontaneous hypertension. Blood pressures in first-generation offspring.

A breeding colony of two subspecies of African green monkeys has been established in an attempt to develop a strain of nonhuman primates with inherited spontaneous hypertension. Selective breeding of normotensive and hypertensive feral animals has produced over 300 first-generation, colony-born offspring of nine possible types, which were grouped according to parentage. Blood pressures were measured by indirect methods in 335 unanesthetized animals aged 0.5 to 6 years. Analysis of variance and covariance of mean blood pressures of animals aged 0.5 to 6 years indicated significant differences between control and experimental offspring groups (p less than .001) both before and after adjusting for sex, subspecies, age, and body weight. Mean blood pressures of control and experimental (p less than .02) offspring were significantly different from 0.5 to 5 years of age. The slopes of the regression of mean blood pressure on age were significantly different between the control and experimental groups (p less than .001). Multiple linear regression analysis indicated significant differences among blood pressure, body weight, and age (p less than .001) and also between age and weight (p less than .001) between the groups. The relative contributions of age and weight to determining the mean blood pressure differed, however. The results indicate that elevated blood pressures can be detected in offspring with even one parent having elevated blood pressure from as early as 1 year of age and that the tendency to develop elevated blood pressure is transmitted from parent to offspring in this species, thereby providing a strong indication that a hypertensive strain of monkeys can be developed through selective breeding.

Salutary effects of moderate hypothermia on the circulatory and myocardial consequences of acute coronary occlusion in dogs.

The efficacy of moderate hypothermia with rewarming in attenuating the myocardial and circulatory consequences of acute coronary ligation was studied in open-chest, anesthetized dogs. Thirty minutes after ligation of the proximal left anterior descending coronary artery, 14 dogs were surface-cooled to 27 degrees C, maintained at this temperature for 2 hr, rewarmed to normothermic levels, and monitored for an additional hour. Fifteen dogs were maintained for a corresponding time period after coronary ligation at normothermic levels. Dogs maintained normothermic demonstrated significant depression (from preligation values) of dP/dt, cardiac output (CO), stroke volume (SV), and left ventricular stroke work and power (LVSW, LVSP) at elevated levels of left ventricular end-diastolic pressure (LVEDP). Dogs subjected to the hypothermic procedure demonstrated decreased inotropic status during hypothermia, but with rewarming, exhibited significantly greater values of left ventricular pressure, dP/dt, CO, SV, LVSW, and LVSP at lower values of LVEDP than observed in dogs maintained normothermic. Increased dysrhythmic activity was not observed during hypothermia. Hearts from dogs subjected to the hypothermic protocol demonstrated qualitatively greater dehydrogenase activity both at the periphery and in the center of the nonperfused region. The results suggest that moderate hypothermia during evolving myocardial infarction may preserve left ventricular cardio- and hemodynamics and thus may be useful in delaying morphological and functional deterioration until definitive treatment can be instituted.

Noninvasive measurement of blood pressure in African green monkeys (Cercopithecus aethiops).

Indirect measurements of arterial blood pressure were made in African green monkeys (Cercopithecus aethiops) employing a Doppler ultrasound stethoscope and standard cuff and an Infrasonde automatic blood pressure recorder. Measurements were obtained from anesthetized (10 mg/kg ketamine (HCI) and unanesthetized (1.5 mg/kg ketamine HCI) animals. Ketamine had no significant effect on blood pressure. Indirect measurements from the brachial artery were compared with direct femoral artery measurements and with each other. Systolic blood pressures measured by the Doppler (r = .948) and Infrasonde (r = .920) methods correlated closely with direct measurements but were significantly lower than systolic blood pressures measured by the direct method. Diastolic blood pressures measured by the Infrasonde method agreed closely with direct measurements (r = .947). Systolic blood pressures measured by the indirect methods correlated closely in both anesthetized (r = .973) and unanesthetized (r = .834) animals and were not significantly different. Mean blood pressures calculated from direct and Infrasonde measurements also correlated closely (r = .963), with direct measurements being 4 mmHg higher on the average. Mean blood pressures are less influenced by methodology and are more reproducible than other pressures. These noninvasive methods can be used to obtain simple and accurate measurements of blood pressure from anesthetized and unanesthetized monkeys and are of value in long-term studies in monkeys.

Cardiac electrical resultant dipole moment of spontaneously hypertensive rats.

The cardiac electrical resultant dipole moment (RDM) of 17 spontaneously hypertensive rats (SHR) was compared with that of 17 Wistar-Kyoto rats (WKY), 65-100 days of age. Relative to body weight, left ventricular weight was 23% greater and right ventricular weight was 18% greater for SHR than for WKY. Left ventricular wall thickness was 11% larger and myocyte diameter was 13% larger for SHR than for WKY. RDM orientation for SHR was more dorsal, leftward, and cranial from middle to end of qRS. The second spatial magnitude peak of QRS, M2, was significantly smaller for SHR than for WKY (P less than 0.001) whereas M3 for SHR was significantly greater than for WKY (P less than 0.001). The alterations in RDM of SHR are greater than can be accounted for simply on the basis of increased cell size. The excitation sequence for SHR might be different from that of WKY. Results show the necessity of considering the details of the spatial magnitude curve during QRS.

Cardiovascular characteristics in adolescents who develop essential hypertension.

The risk parameters for the development of essential hypertension (EH) were evaluated in a group of adolescents with borderline hypertension. A population comprised of 50 adolescents with systolic or diastolic blood pressure between the 90th and 95th percentile was compared to a normotensive (less than 90%) family history-negative control population. Evaluative parameters included genetic risk, resting blood pressure, resting heart rate, and cardiovascular response to mental stress. In a follow-up period of up to 41 months, 28 borderline hypertensive adolescents (56%) developed fixed EH. At the time of initial evaluation, these 28 hypertensive adolescents had a strong family history of EH, higher resting heart rate (p less than 0.01) and blood pressure (p less than 0.01), and a greater cardiovascular response to mental stress (p less than 0.001) compared to the normotensive family history-negative control population. Time series analysis of the stress phase also demonstrated a rhythmic cardiovascular response in the normotensive group (p less than 0.05) that was not present in the hypertensive group. These results indicate that adolescents with borderline hypertension displaying these characteristics have a greater risk for EH than previously reported.

Effects of PEEP and of increased frequency of ventilation during CPR.

Previous reports have attributed increased carotid blood flow to lung ventilation during CPR. This study was undertaken to determine whether PEEP (20 torr airway pressure) or increased frequency of ventilation (3:1) improved arterial pressure, flow, and blood gases. Thirty-three domestic pigs were studied using three protocols (standard 5:1 CPR, 5:1 CPR plus PEEP, 3:1 CPR) distributed such that comparisons could be made between groups as well as within the same pig. For intrapig comparisons, PO2 was significantly improve (p less than 0.05) by PEEP (delta PO2 = 9.7 +/- 13.0 torr). PCO2 was significantly less (p less than 0.005) for 3:1 compared to 5:1 (delta PCO2 = -4.7 +/- 2.1 torr). For group comparisons, PO2 was 55.5 +/- 12.9 torr without and 70.1 +/- 16.3 torr with PEEP (p less than 0.025). For 3:1, PO2 was 66.3 +/- 11.6 torr that was greater (p less than 0.10) than for 5:1. When ventilation was temporarily halted, phasic changes in flow with ventilation were replaced by nearly constant flow approximately equal to maximal flow when ventilation was provided. PEEP and more frequent ventilation improved blood oxygenation but at the expense of carotid blood flow.

Recovery of monkeys after myocardial infarction with ventricular fibrillation. Effects of PGB.

PGBx, a polymeric, stable, free radical derivative of 15-keto-prostaglandin B1, that conserves oxidative phosphorylation in mitochondria under degenerative conditions in vitro, affected survival of male Rhesus monkeys (5-9 kg) anesthetized with pentobarbital and subjected to coronary ligation and induced ventricular fibrillation (VF). In tests performed in sequence with intervening periods for recover, intracardiac injections of norepinephrine (NE), cardiac massage (CM), and electrical defibrillation (EDF) were used to restore cardiac function both in controls and experimental animals, but the latter were injected also with 1 mg/kg PGBx. Recovery was established by maintenance of effective blood pressure without exogenous support. In the control group the cumulative survival for fibrillation episodes of 4, 6, 8, and 12 min was 60, 40, 31, and 25% respectively. In the PGBx-treated group survival for equivalent periods was 100, 93, 93, and 88% respectively. In separate studies, African Green monkeys were subjected to single episodes of VF of either 8 or 12 min. Combined survival was 36% for the controls, 93% for the PGBx-treated animals. Clearly PGBx radically improved cardiac recovery after circulatory arrest due to VF in the presence of acute myocardial infarction. The results also suggest a synergistic action between norepinephrine and PGBx in achieving such recovery.

Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart.

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.

Cardiovascular response to mental stress in normal adolescents with hypertensive parents. Hemodynamics and mental stress in adolescents.

The hemodynamic response to mental stress (mental arithmetic) was studied in adolscents with varying risk factors for essential hypertension (EH), One group (genetic) consisted of normotensive well adolescents who had at least one parentnt with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one pare with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (P less than THE CONTROL POPULATION (P LESS THAN 0.001). The stress response of the normotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p less than 0.001, less than 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension.

The difference vector: assessment of effects of changes or interventions.

Vector dipole moments were measured on young pigs before and one week after ligation of the left anterior descending coronary artery. Vectors were obtained for the three peaks of vector spatial magnitude, M. Preoperative, postoperative, and difference vectors were measured for each peak. If excitation is normal except through the infarcted tissue, the difference vector should be more closely related to the infarct because the normal excitation cancels out. It was found that the postoperative vector was changed by the infarct but that the difference vector was a better indication of infarction. This paper was designed to introduce the method using experimental data for a small number of pigs.

Magnitude, direction and location of the resultant dipole moment of the pig heart.

Vectorcardiograms were obtained from 50 young domestic pigs using the Nelson lead system. Compensation for body size and shape is achieved and the resultant dipole moment magnitude reflects heart size. A strong relationship was found between heart size and maximum magnitude. Dipole moment magnitude increased as four pigs increased from five to ten weeks of age. The dipole moment during QRS is considered in light of known pig heart excitation pattern. Dipole locations during QRS, calculated by computer solution of the Gabor-Nelson equations, were in agreement with heart location and excitation data.