Efficacy of danazol in the control of hormonal migraine.

Of 131 women with hormonally related migraines unresponsive to standard medication, 67 (51.1%) noted profound relief after a 12-month, phased study using danazol for migraine prevention. The first three phases consisted of two-month cycles: dietary control and acetazolamide, the addition of danazol and danazol discontinuation. Eighty-three women (63.36%) reported control of their hormonal migraines while using danazol. In phase IV, 81 women whose headaches were controlled by danazol restarted danazol for an additional six months. Sixty-seven (82.7%) reported continued success with this medication. Danazol proved highly successful in the control of women's cyclic migraine. Its effectiveness remained consistent throughout the treatment course. In the prophylactic treatment of women's hormonal migraine, 400 mg of danazol administered daily for 25 days each month can prove effective when standard medical therapy fails. Furthermore, the response to danazol supported the concept that hormonal migraine should be treated as a distinct clinical entity.

Breath-by-breath measurement of oxygen consumption and FIO2-FEO2 with increased oxygen demand.

Continuous on-line breath-by-breath measurement of pulmonary gas exchange was used to monitor the increase in oxygen uptake (VO2) and carbon dioxide excretion (VCO2) induced by the oxidative phosphorylation uncoupling agent 2, 4-dinitrophenol (DNP) in 10 dogs. With incremental doses of DNP totaling 5 mg/kg, the continuously monitored VO2 increased within 2-3 min after the first injection of the drug. VCO2 showed a similar response 4-6 min after the first injection. Temperature increase due to the pharmacological oxidative phosphorylation uncoupling required 20-30 min for a discernible change at this dose. This study also demonstrated a modified and compromised response to the drug in dogs where oxygen delivery was limited by mechanical ventilation.

Dopamine and dobutamine induce hypokalemia in anesthetized dogs.

Epinephrine-induced hypokalemia appears to be mediated by beta 2-agonist activation of Na+/K+ ATPase. To determine whether dopamine and dobutamine induce hypokalemia, eight adult mongrel dogs were anesthetized and studied in random crossover fashion. Potassium [K+] was measured with an ion-selective microelectrode, and central hemodynamics were measured continuously. After stabilization, dopamine and dobutamine were infused at doses of 2, 4, 8, and 20 micrograms/kg/min (15-min increments/dose), and 0.9% NaCl was infused at equivalent volumes, with a 1-h washout between treatments. The mean change in [K+] at each infusion rate was compared between treatments among dogs with an adequate hemodynamic response. Among dopamine responders (n = 5), [K+] decreased from 3.74 +/- 0.42 mEq/L at baseline to 3.63 +/- 0.51 at 2 micrograms/kg/min (p less than 0.02) and was not significantly different at higher doses. Among dobutamine responders (n = 7), [K+] decreased from 3.52 +/- 0.74 at baseline to 3.31 +/- 0.87 at 8 micrograms/kg/min (p less than 0.02) and 3.25 +/- 0.86 at 20 micrograms/kg/min (p less than 0.02), and was not significantly different at lower doses. We conclude that dopamine and dobutamine induce significant hypokalemia, consistent with their adrenergic agonist activity, and this may be related to the known arrhythmogenicity of these agents.

Simultaneous computer-calculated carbon dioxide and oxygen direct Fick and dye dilution measurements of cardiac output in dogs.

Cardiac output was measured by both indocyanine green dye dilution and the direct Fick method using computer-calculated values for oxygen consumption and carbon dioxide excretion in eight mechanically ventilated dogs anesthetized with pentobarbital, with either tubocurarine or succinylcholine intravenous drip for neuromuscular relaxation. Sequential measurements were made during the anesthesia and in response to pharmacologically induced increased cardiac output using doxapram hydrochloride (1.5 mg/kg) given intravenously. The purpose of this project was to investigate the accuracy and reliability of the direct Fick measurements during anesthesia using computer-calculated measurements of pulmonary gas exchange and, since, these measurements have not been reported in detail previously, to establish tentative control values for future projects. The correlation of dye and direct Fick measurements of cardiac output during the first hour after induction of anesthesia was very good (r = 0.85 for all dye-carbon dioxide Fick values; r = 0.83 for all dye-oxygen Fick values.

Noninvasive measurement of pulmonary gas exchange during general anesthesia.

Expired gas flow volume (VE), carbon dioxide excretion (Vco2) and oxygen consumption (Vo2) were measured continuously for 2-minute periods at 15-minute intervals during at least 75 minutes of general anesthesia and surgery in clinical patients. Analog tape-recorded outputs from an infrared CO2 analyzer, from a rapid polarographic O2 analyzer, and from a pneumotachograph were subsequently processed by a general purpose digital computer. Values for VE, VCO2, and VO2 in a group of 50 normal paralyzed endotracheally intubated women with balanced N2O-O2-fentanyl anesthesia for lower abdominal surgery compare favorably with the few published reports of similar measurements. The measured response to anesthesia and surgery in most patients included a progressive increase in O2 uptake and a concurrent but not necessarily simultaneous decrease in CO2 output with a consequent decreased respiratory gas exchange ratio (RE).

Transmural mitochondrial differences in myocardium.

Two functional mitochondrial populations with different sedimentation rates (S) were obtained from homogenates of canine myocardium by rate zonal centrifugation using an iso-osmotic Ficoll gradient. To ascertain the origin of these populations, the left ventricular wall of normal myocardium was divided into subepicardial (outer one-third), intermediate (middle on-third), and subendocardial (inner one-third) layers. The slow S mitochondria comprised 75% of the mitochondrial population of the subepicardial layer. In contrast, the fast S mitochondria contributed 65% of the subendocardial population. Intermediate layer mitochondria resembled those of the subepicardium. Mitochondria isolated from the three layers had approximately the same density, as shown by isopycnic zonal centrifugation. These studies indicate that mitochondria from subepicardial and subendocardial layers of normal myocardium differ in size and shape but not in density. Electron micrographs (EM) of the subepicardium showed many mitochondria as long as 4 to 8 sarcomeres. Mitochondria from the outer and inner layers of normal myocardium had the same oxidative phosphorylation parameters. Acute myocardial infarction, lasting 1 or 2 hr, resulted in the selective loss of the fast S mitochondria. Because the fast S mitochondria are prevalent in the subendocardium, these results may explain the greater vulnerability of this layer to anoxia.

Demonstration of lack of persistence of effectiveness of intra-aortic balloon pumping of short duration in acute myocardial ischemia.

Experimental studies were carried out to quantitate the effectiveness of intra-aortic balloon pumping (ABP) in reducing severity and extent of myocardial ischemia and the persistence of induced changes after cessation of pumping. Ligation of the anterior descending coronary artery was followed by one hr of observation, IABP for one hr (12 dogs) or 3 hrs (12 dogs) and an additional one hr of observation. Epicardial mapping utilizing 20 electrodes was used to obtain the ST segment elevations (Sigma ST) and numbers of electrodes showing ischemic ST CHANGES (NST) in each group. Reductions of SigmaST of approximately 15% and 33% and reduction of NST of 15% and 20% was observed in the one and 3 hr groups respectively, and persisted throughout the period of pumping. Both parameters were noted to increase within 5 mins after cessation of IABP in both groups. SigmaST frequently rose to almost pre-IABP values in the group pumped for one hr. The group pumped for 3 hrs showed SigmaST increase of approximately 15% and NST increase of approximately 16%. Hemodynamic measurements showed in both groups a mean systolic unloading of approximately 10% and 10-20% mean diastolic augmentation. In conclusion, IABP of short duration (1-3 hrs) early after the onset of acute ischemis (one hr) induces a significant but transient decrease in SigmaST and NST, which reflects a reduction in myocardial ischemia. Further study is required to evaluate the effectiveness of intra-aortic balloon pumping, if intitated several hours after the onset of ischemia, to reproduce the clinical reality of a patient with an acute myocardial infarction.