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Biomedical subjects

R B Laravuso

Publications and source records attributed to R B Laravuso.

9 recordsLinked to original sources

Differential effect of ketamine on cholinergic- and noncholinergic-induced contractions of isolated guinea-pig bronchi.

Ketamine, 3 X 10(-4) M, was found to inhibit transmural electrical stimulation-induced contractile responses of the mainstem and hilar bronchi isolated from reserpine-pretreated guinea-pigs. This concentration of ketamine did not cause direct smooth muscle relaxation in these preparations and a smaller concentration (3 X 10(-5) M) was ineffective in blocking contractions. The pattern of inhibition produced by ketamine was similar to that produced by atropine, 1 X 10(-6) M, in both preparations and was observed at the larger stimulation frequencies employed. When studied in the presence of atropine to optimize noncholinergic-induced contractions, ketamine did not antagonize contractile responses to transmural electrical stimulation. After pretreatment of the isolated tissues with capsaicin, 1 X 10(-6) M, to optimize cholinergic-induced contractions, ketamine produced inhibition of responses to electrical stimulation. Ketamine, 3 X 10(-4) M, produced a shift to the right of the dose-response curve without altering the maximum contractile responses to carbachol, but had no effect on dose-response curves to substance P, the putative noncholinergic transmitter in these bronchial segments. The data suggest that ketamine exerts a selective inhibitory effect on cholinergically mediated contractions in guinea-pig bronchi and that this antagonism is largely exerted post-junctionally, at the level of the smooth muscle muscarinic receptors.

Animals

Pharmacological evidence that human intralobar airways do not contain different receptors that mediate contractions to leukotriene C4 and leukotriene D4.

Contractile responses to leukotriene (LT)C4, LTD4 and LTE4 were examined in intralobar airways from human lung obtained after surgical resection. In addition, the ability of the LT receptor antagonist FPL55712 to antagonize responses to LTC4 and LTD4 was quantified (by calculating -log molar KB values) under experimental conditions designed to minimize metabolic transformation of the LTs. In the absence of drug pretreatment, the three peptide LTs were approximately equipotent and produced similar maximum degrees of contraction. L-Serine borate complex, 45 mM, used as an inhibitor of the degradation of LTC4 to LTD4 by the enzyme gamma-glutamyl transpeptidase, in paired airway segments (adjacent segments from the same branch), produced a small degree (about 3-fold) of shift to the right of the dose-response curve and reduction of the maximum response to LTC4. L-Cysteine, 3 mM, used as an inhibitor of the degradation of LTD4 to LTE4 by the enzyme aminopeptidase, in paired segments, did not alter the dose-response effects of LTD4 or appear to further alter the dose-response effects of LTC4 when applied together with L-serine borate complex in unpaired (nonadjacent) segments. The -log molar KB value for FPL55712 (about 6) was similar for antagonism of responses to both LTC4 and LTD4 in the absence or presence of treatment with the metabolic inhibitors L-serine borate complex, L-cysteine or a combination of the two treatments. The results suggest that inhibition of the enzymes involved in the pathway from LTC4 to LTE4 has little consequence in human airways because the three peptide LTs are approximately equipotent.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid

Left ventricular function during aortic surgery.

Fourteen patients undergoing surgery for aneurysm or occlusive disease of the abdominal aorta were studied. Thirteen patients had a history of hypertension or myocardial infarction; two patients had chronic obstructive pulmonary disease. Tachycardia, hypertension, and elevated pulmonary artery occluded. (PAo) pressure occurred in response to laryngoscopy and intubation in two patients; elevation of PAo pressure in response to aortic cross-clamping occurred in two patients. In three of these four patients, electrocardiographic evidence of myocardial ischemia appeared. These events are important in a consideration of the occurence of myocardial infarction in patients undergoing abdominal aortic surgery. Satisfactory treatment of myocardial ischemia has been accomplished with the use of propranolol hydrochloride and sodium nitroprusside.

Aged

Distribution of ventilation-perfusion ratios in dogs with normal and abnormal lungs.

We have recently described a new method for measuring distributions of ventilation-perfusion ratios (VA/Q) based on inert gas elimination. Here we report the initial application of the method in normal dogs and in dogs with pulmonary embolism, pulmonary edema, and pneumonia. Characteristic distributions appropriate to the known effects of each lesion were observed. Comparison with traditional indices of gas exchange revealed that the arterial PO2 calculated from the distributions agreed well with measured values, as did the shunts indicated by the method and by the arterial PO2 while breathing 100 per cent 02. Also the Bohr dead space closely matched the dispersion of ventilation in realtion to VA/Q. Assumptions made in the method were critically evaluated and appear justified. These include the existence of a steady state of gas exchange, an alveolar-end-capillary diffusion equilibration, and the fact that all of the observered VA/Q inequality occurs between gas exchange units in parallel. However, theoretical analysis suggests that the method can detect failure of diffusion equilbration across the blood-gas barrier should it exist. These results suggest that the method is well-suited to clinical investigation of patients with pulmonary disease.

Acute Disease

Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100 per cent O2.

A new method has been developed for measuring virtually continuous distributions of ventilation-perfusion ratios (V(A)/Q) based on the steadystate elimination of six gases of different solubilities. The method is applied here to 12 normal subjects, aged 21-60. In nine, the distributions were compared breathing air and 100% oxygen, while in the remaining three, effects of changes in posture were examined. In four young semirecumbent subjects (ages 21-24) the distributions of blood flow and ventilation with respect to V(A)/Q were virtually log-normal with little dispersion (mean log standard deviations 0.43 and 0.35, respectively). The 95.5% range of both blood flow and ventilation was from V(A)/Q ratios of 0.3-2.1, and there was no intrapulmonary shunt (V(A)/Q of 0). On breathing oxygen, a shunt developed in three of these subjects, the mean value being 0.5% of the cardiac output. The five older subjects (ages 39-60) had broader distributions (mean log standard deviations, 0.76 and 0.44) containing areas with V(A)/Q ratios in the range 0.01-0.1 in three subjects. As for the young subjects, there was no shunt breathing air, but all five developed a shunt breathing oxygen (mean value 3.2%), and in one the value was 10.7%. Postural changes were generally those expected from the known effects of gravity, with more ventilation to high V(A)/Q areas when the subjects were erect than supine. Measurements of the shunt while breathing oxygen, the Bohr CO(2) dead space, and the alveolar-arterial oxygen difference were all consistent with the observed distributions. Since the method involves only a short infusion of dissolved inert gases, sampling of arterial blood and expired gas, and measurement of cardiac output and minute ventilation, we conclude that it is well suited to the investigation of pulmonary gas exchange in man.

Acetone