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Biomedical subjects

M W Perkins

Publications and source records attributed to M W Perkins.

9 recordsLinked to original sources
PubMed1994

The role of protein kinase C in lipopolysaccharide-induced myocardial depression in guinea pigs.

The effect of lipopolysaccharide (LPS) on cardiac protein kinase C (PKC) activation and cardiac depression was evaluated. Guinea pigs (n = 44) received intraperitoneal injections of saline or Escherichia coli LPS (2 mg/kg). Left atria were harvested 16 h later and suspended in oxygenated low calcium (1 mM) (n = 24) or high calcium (5 mM) (n = 20) 30 degrees C Krebs-Henseleit buffer. Atria were treated with H-7 (n = 23), a PKC inhibitor, or vehicle (n = 21). Contractile responses to changes in preload and stimulating frequency, in the resting and potentiated states, and to escalating doses of phenylephrine were measured. PKC activation in ventricular muscle was also determined. LPS activated ventricular PKC (p < .05) but treatment with H-7 failed to reverse LPS-induced atrial dysfunction in the low calcium buffer. Contractile function in the potentiated state indicated that LPS appears to interfere with calcium release from the sarcoplasmic reticulum (SR). The contractile response to phenylephrine was markedly attenuated in atria harvested from endotoxic animals. These data indicate that LPS-induced cardiac depression is mediated, in part, by alterations in SR calcium release. LPS activates cardiac PKC but a causal relationship among LPS, PKC, and cardiac dysfunction remains to be established.

Animals↗
PubMed1992

Tumor necrosis factor-alpha causes myocardial depression in guinea pigs.

BACKGROUND AND METHODS: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of metabolic and cardiovascular derangements in sepsis and endotoxicosis. We tested the hypothesis that TNF-alpha causes myocardial depression and alters the cardiac responsiveness to administered norepinephrine. Albino Hartley guinea pigs (n = 32) of either sex were injected iv with saline (1.5 mL) or recombinant human TNF-alpha (1 mg/kg). At 6, 24, or 72 hrs after injection, atria were harvested, split, connected to force displacement x transducer-amplifier-recorder systems and maintained in vitro in oxygenated 37.5 degrees C Krebs-Henseleit buffer. RESULTS: Maximal left atrial force of contraction and maximal left atrial velocity of contraction were decreased in the TNF-alpha treated animals compared with controls (p less than .05), irrespective of time after TNF-alpha injection. There were no differences between groups for left atrial maximal velocity of relaxation and right atrial rate. The norepinephrine concentration that elicited a 50% maximal left atrial contractile response (ED50) was higher in TNF-alpha treated animals compared with controls (p less than .05). Maximal left atrial force of contraction, maximal right atrial rate, and right atrial ED50 were similar in the two groups. CONCLUSIONS: These results indicate that TNF-alpha injected in vivo causes in vitro myocardial depression and alters cardiac responsiveness to norepinephrine.

Analysis of Variance↗
PubMed1989

A model to decrease hepatic blood flow and cardiac output with pressure breathing.

This randomized, controlled, crossover study evaluated the effect of continuous positive airway pressure (CPAP) breathing on hepatic blood flow (HBF) and cardiac output in 10 healthy male subjects. A CPAP mask was placed on the face and the subject breathed at either CPAP 12.5 cm H2O or ambient airway pressure. The estimated HBF was calculated as the ratio of indocyanine green plasma clearance to one minus the hematocrit. Cardiac output was measured with Doppler ultrasound. CPAP caused HBF to decrease in 8 of 10 subjects (14.1% +/- 15.3%, mean +/- SD, p = 0.033) and cardiac index (CI) to decrease in all subjects (14.1% +/- 5.7%, p = 0.0001). Stroke volume and respiratory rate were significantly decreased; heart rate was unchanged. These results indicate that CPAP at 12.5 cm H2O causes a small, but significant decrease in both HBF and CI.

Adult↗
PubMed1989

Physiologic implications of mechanical ventilation on pharmacokinetics.

Numerous factors present in the critically ill patient decrease drug clearance. The contribution of one factor, mechanical ventilation, to this decrease is largely unknown and unquantified. This article attempts to review the physiologic effects of mechanical ventilation and to propose theoretical changes in the pharmacokinetics of concomitantly administered drugs. Mechanical ventilation with or without positive end-expiratory pressure is a well-documented cause of decreases in cardiac output, hepatic and renal blood flow, glomerular filtration rate, and urine flow. The mean airway pressure delivered, the pathophysiologic state of the patient, and coexisting therapeutic interventions affect the degree of hemodynamic alteration. Theoretically, these hemodynamic changes can decrease the clearance of several drugs frequently administered to critically ill patients. Decreased hepatic blood flow decreases the clearance of nonrestrictively cleared drugs. The pharmacokinetics of drugs predominantly renally cleared, by either glomerular filtration or tubular secretion, are affected by a decrease in renal blood flow or glomerular filtration rate. Also, the clearance of agents for which tubular reabsorption is important may decrease because the reduction in urine flow resulting from mechanical ventilation allows increased time for drug reabsorption. Interventions that minimize the decrease in cardiac output and organ blood flow and, theoretically, the risk of the adverse drug reactions from decreased drug clearance include expansion of intravascular volume, administering positive inotropic agents, and decreasing mean airway pressure. Monitoring serum concentration of critical and toxic agents suspected to have altered clearance in patients receiving mechanical ventilation is recommended. We hope that our article will stimulate future research in this area to give clinicians guidelines for drug dosing in patients receiving mechanical ventilation.

Humans↗
PubMed1989

Intraoperative complications in patients receiving amiodarone: characteristics and risk factors.

This article reviews amiodarone's adverse cardiovascular properties, concentrating on those in surgical patients, and evaluates several potential risk factors. Amiodarone has negative inotropic and chronotropic properties as well as peripheral vasodilating properties that may manifest as bradycardia, reduced cardiac output, and hypotension. These reactions are clinically important during surgery, because of resistance to pharmacologic resuscitation and an increased mortality rate. Potential risk factors include ventricular dysfunction, rapid infusion rate, hypocalcemia, cardiopulmonary bypass, general anesthesia, concurrent negative inotropic or chronotropic drugs, and an elevated serum amiodarone or desethylamiodarone concentration. The following measures may decrease the risk of intraoperative adverse reactions in amiodarone-treated patients. The serum calcium concentration should be at the physiologic level and the serum amiodarone and digoxin concentrations should be in the therapeutic range. Negative inotropic and chronotropic agents should be discontinued when possible. A temporary cardiac pacemaker may prevent intraoperative hypotension due to bradycardia. Amiodarone may be discontinued before surgery to minimize the risk of intraoperative complications, but this decision should balance the potential for amiodarone-associated intraoperative complications against the risk of arrhythmia recurrence and the delay of surgery.

Amiodarone↗
PubMed1981

Female homosexuality and body build.

A recent report utilizing self-reported and small-small-size data suggests that group differences in body build between heterosexual and homosexual women are likely to be minor. The data presented in this paper do not support this contention. Interviews were conducted with 241 nonpatient, exclusively homosexual women to determine their socioeconomic status, their psychosexual identification, and their overt sexual behavior patterns. The entire sample was then divided into seven psychosexual/behavioral categories derived from the interview data. Anthropometric data were collected for five subsamples and included (1) height measurements, (2) biacromial and bi-iliac measurements, (3) androgyny scores, (4) arm and leg girth measurements, (5) bicondylar diameters of the femur and humerus, (6) triceps, subscapular, and suprailiac skinfolds, and (7) somatotype profiles. These data indicate that the homosexual women have narrower hips, increased arm and leg girths, less subcutaneous fat, and more muscle than heterosexual women.

Adolescent↗