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Biomedical subjects

J T Watson

Publications and source records attributed to J T Watson.

At least 145 records · Page 8Linked to original sources

Intraaortic balloon counterpulsation in patients in cardiogenic shock, medically refractory left ventricular failure and/or recurrent ventricular tachycardia.

Of the 27 patients described, 23 were in cardiogenic shock, 2 had severe left ventricular failure, and 2 had medically refractory ventricular tachycardia. Utilizing intraaortic counterpulsation, adequate systemic blood pressure was initially restored in 19 patients. Nine of these were subsequently weaned from circulatory assistance, but only three were discharged from the hospital and are currently alive. The remaining 10 patients who derived initial benefit from circulatory assistance were balloon-dependent in that they could not be weaned from circulatory assistance. Eight of these patients subsequently underwent cardiac catheterization; four had inoperable disease. The remaining four patients underwent surgery for either resection of the area of infarction and/or for myocardial revascularization; only one survived to subsequently leave the hospital. Ventricular volumes were abnormal and ejection fractions were below 30 per cent in all the patients in cardiogenic shock except one who underwent cardiac catheterization and ultimately died. Ejection fractions were greater than 30 per cent in the two patients with cardiogenic shock who were weaned from balloon support and survived to leave the hospital without surgery. Both of these patients had inferior myocardial infarction. The data obtained from this experience suggest that intraaortic counterpulsation is a very useful adjunct to currently existing medical measures to treat both cardiogenic shock and medically refractory left ventricular failure but that most patients have such extensive disease that they can neither be weaned from balloon support nor undergo successful infarctectomy or myocardial revascularization.

Adult↗

Evidence for a new mineralocorticoid in patients with low-renin essential hypertension.

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.

Adrenalectomy↗

Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.

Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordi) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and modified the reduction in the reflow phenomenon to the subendocardial portion of the ischemic area. Thus, both an increase in coronary vascular resistance and a significant reduction in reflow to the subendocardial portion of the ischemic area occur in the canine heart after 120 minutes of myocardial ischemia. Moreover, the increase in coronary vascular resistance can be prevented and the reduction in reflow to the subendocardial portion of the ischemic area can be modified by the administration of hypertonic mannitol.

Animals↗

Urinary prostaglandins. Identification and origin.

Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.

Angiotensin II↗

The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling.

Acute Disease↗

Biomedical applications of vapor phase analysis.

Recent investigations of physiological systems have demonstrated that even minor chemical constituents can play a major role in mediating physiological responses. Recognizing this, the investigator seeks to isolate or selectively quantify the concentration of a specific drug or hormone that is available to target tissue. Today, as drugs are developed which are more and more potent, greater demands are made on analytical methodology for ever more sensitive yet specific techniques of quanification. The techniques of vapor phase analysis such as gas chromatography, especially in combination with mass spectrometry, offer great promise to investigative pharmacology/toxicology. Some of the potentials and limitations of vapor phase analysis will be described. More detailed descriptions of basic gas chromatography (McNair and Bonelli, 1969; Ettre and McFadden, 1969) and combined gas chromatography-mass spectrometry (McFadden, 1973) can be found elsewhere.

Blood Chemical Analysis↗

Five-day partial bypass using a membrane oxygenator without systemic heparinzation.

These studies indicate that a heparin bound membrane oxygenator can be used in venovenous bypass circuit in dogs for a period of 5 days without systemic heparinization. The plasma SGOT, plasma hemoglobin, and MLW of the animals increased after initiation of bypass but returned to control levels. Oxygen transfer did not deteriorate in the membrane oxygenator, eliminating the necessity of membrane exchange during the 5-day bypass.

Animals↗