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Biomedical subjects

N D Kien

Publications and source records attributed to N D Kien.

27 records · Page 2Linked to original sources

Decrease in vascular resistance in the isolated canine hindlimb after graded doses of alfentanil, fentanyl, and sufentanil.

Under halothane anesthesia five dogs were prepared with both hindlimbs isolated from the systemic circulation to allow intermittent placement on extracorporeal perfusion at constant flow. One limb of each dog was surgically denervated. In this relatively anesthetic-free preparation, graded equivalent doses of alfentanil, fentanyl, and sufentanil were infused over 30 s, and vascular resistance was measured. Increasing opioid administration caused a progressive diminution in peripheral resistance. By the high dose level, alfentanil (500 micrograms/kg), fentanyl (50 micrograms/kg), and sufentanil (6 micrograms/kg) caused equal and significant decreases of 48%, 48%, and 44% in resistance, respectively. There was no difference among the opioids in effects on resistance at equivalent dosages. Neither pretreatment with naloxone nor denervation changed the response to the narcotics. We conclude that the three synthetic opioids produce vasodilation by direct action on the peripheral vascular smooth muscle.

Alfentanil↗

Malignant hyperthermia in humans--standardization of contracture testing protocol.

Malignant hyperthermia (MH) diagnostic biopsy centers across North America have not previously been standardized in regard to protocols and specific muscles. Recent standardization criteria prompted this study of the vastus and rectus abdominis muscles. This study evaluated changes in contracture tension after electrical stimulation of 271 bundles taken from the vastus (n = 16) and rectus abdominus (n = 19) muscle biopsies of normal individuals when exposed to tissue baths in the absence of and in the presence of caffeine (0.5, 1.0, 2.0, 4.0, 8.0, and 32.0 mM) alone, halothane (1% or 3%) alone, or the combination of halothane (1%) plus caffeine (0.25, 0.5, 1.0, 2.0, 4.0, and 32.0). Caffeine threshold concentration was that concentration of caffeine that produced a 7% increase in tension. Caffeine specific concentration (CSC) and halothane caffeine specific concentration (HCSC) were those concentrations of caffeine alone or of halothane plus caffeine that produced a 1 g increase in tension. The concentration of caffeine alone that increased the contracture tension by 7% averaged 6.7 +/- 0.3 mM for vastus, significantly greater than 4.1 +/- 0.2 mM for the rectus muscle biopsies. Caffeine specific concentration was significantly greater for vastus muscle (7.7 +/- 0.7 mM) than it was for rectus muscle (4.9 +/- 0.4 mM). Three percent halothane alone showed contractures in 3/41 vastus (all less than 0.5 g) and 18/54 rectus muscle bundles (8 greater than 0.5 g). Mean HCSC was statistically significantly greater for vastus muscle (1.9 +/- 0.2 mM) than for rectus muscle (1.2 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Cardiac performance following hypertonic saline.

The present study was undertaken to examine cardiovascular function before and after either intravenous or intra-arterial infusion of hypertonic saline (7.5% NaCl) in halothane-anesthetized dogs. A high-fidelity micromanometer and ultrasonic dimension transducers were implanted to measure pressure and wall motion of the left ventricle (LV). Cardiac output (CO) was measured using an electromagnetic flowmeter and thermodilution. The slope (Ees) of the linear regression of the LV pressure-diameter relationship was used as an index of cardiac contractility. Intravenous infusion of hypertonic saline (3 ml/kg) increased mean arterial pressure (MAP, 104 +/- 6 to 116 +/- 6 mmHg), heart rate (HR, 124 +/- 21 to 140 +/- 13 bpm), CO (3.2 +/- 0.9 to 4.2 +/- 0.5 l/m) and Ees (11.6 +/- 2.1 to 14.8 +/- 1.9 mmHg/mm). Systemic vascular resistance (SVR) fell by 18%. The above responses were similar whether infusion was intravenous or intra-arterial into innervated or denervated hind limbs. While nerve blockade at T-4 (xylocaine) attenuated the changes in CO and SVR and completely prevented the tachycardia, the inotropic response remained intact. These studies suggest that the cardiac effects of hypertonic saline infusion are not mediated by pulmonary or peripheral osmoreceptors and the increased contractility may result from a direct myocardial effect of increased osmolality.

Animals↗

Intracranial pressure increases during alfentanil-induced rigidity.

Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.

Alfentanil↗

The influence of adenosine triphosphate on left ventricular function and blood flow distribution during aortic crossclamping in dogs.

To evaluate the influence of adenosine triphosphate (ATP)-induced vasodilation on myocardial performance and blood flow during aortic crossclamping (XC), ten dogs were instrumented to measure left ventricular (LV) pressure and dimensions. Regional LV function was assessed from the percentage of systolic shortening, whereas the slope of the linear regression of the LV end-systolic pressure-diameter relationship was used as an index of overall contractility. The regional blood flow distribution was measured from sequential injections of radioactive microspheres. Following XC, systemic arterial pressure proximal to the clamp (SAPa), LV end-diastolic pressure (LVEDP), LV end-systolic meridional wall stress (WS), and central venous pressure (CVP) increased significantly, whereas the cardiac index (CI) and heart rate did not change. After 30 minutes of ATP infusion (1 mg/kg/min) SAPa, LVEDP, WS, and CVP returned to control levels, CI increased significantly compared with XC alone, and vascular resistance fell below the control level. ATP produced a threefold increase in myocardial blood flow and shifted the intramural distribution in favor of the endocardial layer. In conclusion, our investigation of the effect of ATP on aortic XC in a canine model showed the drug to produce a smooth, predictable, and rapid reduction in left ventricular preload and afterload. This was accomplished with minimal changes in distal organ perfusion, some improvement in measured cardiac performance, and a large increase in myocardial blood flow.

Adenosine Triphosphate↗

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog.

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.

Adenosine Triphosphate↗

Hemodynamic responses to alfentanil in halothane-anesthetized dogs.

Alfentanil is an opioid that has been used both as a sole anesthetic and in conjunction with other inhalation anesthetics. However, its effects on myocardial performance and regional blood flow are not clearly known. Using sonomicrometry and radioactive microsphere techniques, we examined the hemodynamic responses to alfentanil when given as a loading dose (45 micrograms/kg) followed by continuous infusion (3 micrograms X kg-1 X min-1) in dogs anesthetized with halothane. Similar plasma levels of alfentanil were observed after the loading and infusion doses, and both techniques of administration produced a significant reduction in arterial pressure without change in global or regional function of the left ventricle. Although cardiac output and left ventricular end-diastolic pressure remained unchanged, heart rate and systemic vascular resistance decreased significantly after the loading dose and recovered slightly when alfentanil was infused continuously. Despite the systemic hypotension, alfentanil did not alter perfusion to the heart, brain, muscle, and skin; however, blood flow to the renal cortex and the arterial supply to the liver decreased by 25 and 60%, respectively. Reduction in blood flow to the kidneys and the liver suggests that alfentanil should be used with caution when normal function of these organs is in question.

Alfentanil↗