The effect of age on active and cryoactivatable inactive plasma renin levels was examined in 58 normal subjects and 58 patients with essential hypertension during recumbency and after stimulation with furosemide and ambulation. Active renin levels declined with age in both supine subjects and patients. Inactive renin levels did not change with age in normal subjects, while in hypertensive patients they decreased with age. Following stimulation with furosemide and ambulation, the levels of active renin increased but its responsiveness to the stimulus decreased with age in both groups. In contrast, inactive renin was not significantly influenced by furosemide administration and ambulation. These data show that an acute stimulation with furosemide and ambulation affects mainly the active form of plasma renin, and that the effect of age on inactive plasma renin in normal subjects may be different from that in patients with essential hypertension.

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In an attempt to correlate xanthomas with atherosclerosis, the characteristics of serum lipid and lipoprotein profiles are explored in xanthoma patients. Xanthomas are classified into 5 subtypes: xanthelasma, planar xanthoma, papulo-eruptive xanthoma, tuberous xanthoma and tendon xanthoma. The clinical characteristics of xanthoma patients are summarized in the following, 1) Xanthelasma in 2 different types: one normolipemic and the other hyperlipidemic; of 30 xanthelasma patients, 5 were normolipemic. one of them had low HDL-cholesterol. 2) Tuberous and tendon xanthomas were all hypercholesterolemic, with serum cholesterol above 300 mg/dl and LDL-cholesterol above 255 mg/dl, while HDL-cholesterol was within normal range. 3) The xanthoma patients were generally not obese. 4) Their laboratory findings often showed such abnormalities as elevated levels in serum fibrinogen, LDH, CPK and uric acid. The resemblance of the clinical characteristics between xanthomas and atherosclerotic vascular disease, e.g., myocardial infarction, was striking. If the causation of their common tissue alterations by lipid accumulation is pathologically and biochemically defined, the correlation between those 2 kinds of disease can be. established.

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Plasma norepinephrine (NE) concentration was measured in blood samples from the pulmonary artery (PA), the superior vena cava (SVC), the inferior vena cava (IVC) and the femoral artery (FA) in 34 patients undergoing diagnostic cardiac catheterization. In patients with pulmonary hypertension, the mean plasma NE concentrations in PA, SVC and FA were significantly higher than that of IVC, but no such difference was found in patients without such hypertension. Except in IVC, the plasma NE concentration in patients with pulmonary hypertension was significantly higher than in others. Furthermore, the plasma NE concentration was positively correlated with the mean pulmonary arterial pressure and inversely related to pulmonary arterial oxygen saturation in patients without a shunt. These results suggest the possibility that vasoconstriction by the sympathetic nervous system may contribute to the development of pulmonary hypertension in patients without the shunt.

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The myocardial norepinephrine (NE) content and glycogen phosphorylase activity were measured before and after coronary artery ligation in dogs anesthetized with pentobarbital. Coronary artery ligation was performed by ligating a branch of the left anterior descending coronary artery (LAD). Before coronary artery ligation, the NE content in the circumflex area (778.05 ± 37.83 ng·g^-1 wet tissue) was significantly higher than that in the LAD area (630.57 ± 35.75 ng·g^-1 wet tissue). The NE content in the circumflex area (non-ischemic area) decreased significantly 1.5, 3, 30, 60, and 420 min after coronary artery ligation, while that in the LAD area (ischemic area) did not decrease significantly except for the NE level obtained after 420 min of coronary artery ligation. The glycogen phosphorylase activity increased significantly 1.5 min after coronary artery ligation in both non-ischemic and ischemic areas. From the foregoing results, it is suggested that NE release occurs in both ischemic and non-ischemic areas within at least 1.5 min after coronary artery ligation, and that within 60 min after coronary artery ligation the NE content decreases in the non-ischemic area but not in the ischemic area probably because of very limited washout of the released NE in the ischemic area.

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Changes in the cardiac sarcolemma in myocardial infarction were studied by both determination of Na⁺-K⁺-ATPase activity and SDS gel electrophoretic analysis of sarcolemmal proteins in the canine heart. Nlnety minutes after coronary ligation. Na⁺-K⁺-ATPase activity in ischemic myocardium was decreased significantly to approximately 36% of that of non-ischemic myocardium, and it remained at the lower level for 28 days. By SDS gel electrophoresis, reduction of the protein band with molecular weight of 111.000, which is suggestive of the main component of ATPase, was observed simultaneously with the reduction of Na⁺-K⁺-ATPase activity. These results indicate that ischemia for 90 minutes produces substructural changes in the sarcolemma indicating irreversible myocardial changes.

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5'-Nucleotidase activity in the cerebrovascular system in stroke-prone spontaneously hypertensive rats was histochemically investigated. In the hypertensive rats, an enhancement of 5'-nucleotidase activity was observed already in the early stage of hypertension and the anzyme activity increased with advancing age. The enzyme activity appeared earlier and stronger in the larger arteries in the basal portion than the pial arteries in the convexity of the brain and arterioles in the brain parenchyma. The activity in the arterial walls proved to be particularly strong in the thickened parts showing cellular hyperplasia, mainly at the branching portions. The reaction products localized along the plasma membrane, and also in the cytoplasma in some parts where the activity was strong. Relationship between the increased 5'-nucleotidase activity and aging of the cells composing the cerebrovasculature resulted from an accelerated or repeated cell proliferation was discussed.

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Parathyroid glands play a significant role in the development of hypertension in spontaneously hypertensive rat (SHR), like in deoxycorticosterone acetate (DOCA) + NaCl model. Parathyroidectomy (PTX) performed after weaning delayed systolic blood pressure (SBP) increase and slowed heart rate (HR) in SHR for 42 weeks. These changes could not be attributed to decrease of serum calcium in PTX animals since supplementation of calcium, rendering serum calcium normal, did not reestablish SBP and HR to those of sham SHR. Moreover, in the thyroparathyroidectomized (TPTX) animals SBP and HR were increased by autotransplantation of parathyroids. When hypertension was established (week 15), PTX produced no more changes on cardiovascular parameters measured. These data clearly indicate that independent of thyroidectomy, PTX leads to a lesser degree of hypertension in young SHR, but was without effect on established hypertension. In conclusion, parathyroid glands are required for total development of the hypertensive process in SHR.

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Thirty open-chest mongrel dogs were studied to characterize mitochondrial respiration in reperfused myocardium following ischemia induced by left anterior descending coronary artery ligation up to 40 minutes. Regional myocardial blood flow was measured by radioactive microspheres: ⁴⁶Sc (9μ) during coronary artery occlusion, ⁸⁵Sr (9μ) during reperfusion. Mitochondria were isolated from endocardial and epicardial layers in both nonischemic and ischemic myocardium Mitochondrial respiration was characterized by a polarographic technique. Cardiac output, stroke volume left ventricular, stroke work and mean arterial pressure were depressed during coronary artery occlusion and they did not improve during 10-20 min of coronary artery reperfusion. Reperfused myocardium following 40 min of coronary artery occlusion increased in myocardial blood flow both in ischemic and non-ischemic tissues. Ratio of phosphorylated adenosine diphosphate to consumed oxygen was unchanged. Ischemic endocardial layer following 40 min of coronary artery occlusion showed depression of respiratory control index at the end of 10-20 min of reperfusion. Mitochondrial state-3 respiration was severely depressed when glutamate was added as substrate at the end of coronary artery occlusion. State-3 respiration recovered to normal level during reperfusion in the myocardium rendered ischemic for less than 30 min; whereas, state-3 respiration was still depressed during 10-20 min of reperfusion following 40 min of coronary artery occlusion. During the reperfusion period, endocardial blood flow was related to mean arterial pressure both in the nonischemic (r= 0.73, p < 0.05) and in the ischemic zone (r=0.72, p < 0.05) in hearts ischemic for less than 30 min Mitochondrial state-3 respiration was not correlated to perfusion pressure in completely reversible (artery ligated < 30 minutes) myocardium. In ischemic endocardial layer following 40 min of coronary artery occlusion, state-3 respiration was related to perfusion pressure [r = 0.88 (p < 0.02) glutamate substrate; r= 0.92 (p < 0.02) succinate substrate] and to the product of heart rate and mean arterial pressure during 10 minutes of reperfusion (r = 0.83, p < 0.04). These results suggest that myocardium can survive up to 30 minutes of severe ischemia. In partially necrotic myocardium, mitochondrial functional recovery was correlated to mean arterial pressure (perfusion pressure) and cardiac rate pressure product in early reperfusion, however, coronary blood flow was not correlated to perfusion pressure in this particular phase.

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The effect of pH 6.4-7.0, a pH known to exist in the ischemic myocardium, was studied on the isolated cardiac sarcoplasmic reticulum (SR) and myofibrils. Oxalate supported SR calcium uptake velocity decreased from 11.0 ± 0.3 × 10^-3 μmoles Ca²⁺/mg·min at pH 7.0 in the whole heart homogenate to 4.4 ± 0.2 × 10^-3 μmoles Ca²⁺/mg·min at pH 6.4 (p < 0.05). Isolated SR calcium uptake velocity decreased from 0.94 ± 0.01 μmoles Ca²⁺/mg·min at pH 7.0 to 0.535 ± 0.015 μmoles Ca²⁺/mg·min at pH 6.4 (p < 0.05) while Ca²⁺-stimulated. Mg²⁺-dependent ATPase activity was unaffected by pH (pH 7.0: 1.10 ± 0.05, pH 6.4: 1.10 ± 0.025 μmoles Pi/mg·min). Efficiency ratio of calcium transport, or the coupling ratio, (μmoles Ca²⁺ transported/μmole ATP hydrolyzed) decreased from 0.87 ± 0.064 at pH 7.0 to 0.507 ± 0.05 at pH 6.4 (p < 0.01). Myofibrillar pCa (-log [free Ca²⁺] ) ATPase activity was unaffected between pH 6.8 and 7.2. At pH 6.6, increasing calcium concentration (pCa < 6.5) inhibited myofibrillar ATPase activity (50% activation at pH 7.0: 6.6, pH 6.6 : 6.3) and this inhibitory phenomenon was accentuated at pH 6.4. It is concluded that pH 6.4-6.6 significantly uncouples calcium transport from ATP hydrolysis in cardiac SR and significantly alters myofibrillar ATPase activity. Comparing these observations with reported pH changes in the ischemic myocardium, it is postulated that increasing proton concentrations can serve as a mediator of contracture in the ischemic myocardium.

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The effect of vitamin E (VE) on arachidonate-induced respiratory distress and sudden death in rats was examined. Fourteen VE deficient rats (VEDR), 11 normal control rats (NCR) and 12 VE supplemented rats (VESR) were injected with sodium arachidonate into the central vein. VEDR developed various arrhythmias, respiratory distress, apnea, hypotension, and 11 out of 14 VEDR (79%) died shortly after the injection. Many of these rats demonstrated obstruction of the small pulmonary vasculature with platelet aggregates. On the other hand, NCR and VESR developed much attenuated respiratory insufficiency and 5 out of 11 (45%) and 2 out of 12 (17%) died respectively. Twenty-six VEDR, 16 NCR and 25 VESR were used for an in vitro study of the platelet and vessel wall. VEDR demonstrated increases in platelet counts and aggregation as compared with NCR and VESR. Lipid peroxide in platelets, plasma and the aorta was significantly increased in VEDR. Prostacyclin-like activity in the aorta was not different among VEDR, NCR and VESR. The above results indicate that the pronounced respiratory distress, high mortality rate and pulmonary microembolism with platelet aggregates in VEDR may be attributed to the increase in platelet number and aggregability. The increased platelet aggregability was suggested to be the result of increased prostaglandin biosynthesis in platelets. The increased lipid peroxidation in vessel wall and plasma might also contribute to the enhanced respiratory distress. The respiratory distress and mortality as well as in vitro laboratory results were not different between NCR and VESR. This study indicates that vitamin E supplementation does not protect against the development of respiratory distress and sudden death induced by arachidonic acid over the normal control rats.

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We report a case of multiple pulmonary embolism with hemolytic anemia. The patient was a 48-year old woman who suffered from cold agglutinin disease with evidence of a recent mycoplasma pneumonia infection. Multiple pulmonary embolism was diagnosed on the basis of her symptoms, serial blood gas studies and ⁹⁹Tc-MAA perfusion lung scan. A recent mycoplasma infection was evidenced by both a 1:64 rise in mycoplasma complement fixation titers and a 1:2048 rise In cold agglutinin titers. The pulmonary embolism was thought to be due to massive intravascular hemagglutination taking place in the presence of cold agglutinin, and the hemolytic anemia with an elevation of IgM immunoglobulin was thought to be autoimmune in nature.

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A relation between the forward and the Inverse problem on electrocardiography Is discussed in the idealized mathematical model: the human body is regarded as a homogeneous conductor and the cardiac generator is a single magnetic current loop.

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A new method of determining epicardial potentials from body surface maps is presented. Epicardial potentials can be estimated via the forward transfer matrix computed by using the finite element method. Due to smoothing and decrease in value in potential distribution of the body surface, the inverse problem involved becomes, in nature, ill-conditioned and direct application of the usual inversion technique will give an extremely oscillatory solution. Therefore, in order to obtain a practically meaningful solution, an appropriate regularizing procedure must be developed and, in the present paper, an effective regularization based on the generalized inverse matrix is proposed and Its usefulness is demonstrated. Numerical experiments suggest that It' the epicardial map includes high components of spatial frequency the Inverted epicardial map will have poor resolution. This is especially true at the epicardial surface distant from the body surface, such as on the diaphragmatic side of the ventricle. If the epicardial maps have to be inverted over the entire region of the epicardium with a clinically allowable accuracy, about 180 body surface lead points and 3 significant figures in the measurements of body surface potentials will be needed.

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For the purpose of determining an appropriate distance of lead points for constructing body surface maps, Fourier analysis was performed on potential distribution reflecting the epicardial breakthrough, and inter-electrode distance necessary for sampling of harmonics contributing to the body surface potential distribution was determined by application of sampling theorem. Potential distribution was simultaneously recorded with an interval of 4 mm for 250 msec along the vertical (head to foot) and horizontal (right to left) line crossing a second-minimum appearing on the chest surface of a healthy adult, and the data obtained from 9.6 cm along the respective lines underwent Fourier transform. Relative contribution of the second harmonics to the original wave forms increased with time lapse after QRS initiation, in accordance with reduction of the first harmonics component, and attained the maximum (32.5% of total power spectrum without d-c component) at the instant of occurrence of the second-minimum. A similar tendency was observed among higher harmonics, but their contribution was comparatively low (within 10%). Inter-electrode distance determined by sampling theorem was 4.8 cm for the first harmonics and 2.4 cm for the second harmonics. In conclusion it is proposed that placement of electrodes with an inter-electrode distance of 2.4 cm is necessary for acquiring clinically important data on the epicardial breakthrough.

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With use of a homogeneous torso model, dipole and quadrupole sensitivity was determined for unipolar leads from many sites on the thoracic surface. Representatives of non-dipolar maps were obtained from the sensitivity of each of unipolar leads to the 5 rectangular components of the quadrupole. Over-all sensitivity to the quadrupole or the magnitude of the lead tensor was calculated from the measurements and mapped over the torso surface. This map indicates relative proximity of the thoracic surface and gives a theoretical basis for the selection of electrode locations in the surface mapping technique.

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