The pharmacology of dichloroacetate

Dichloroacetate (DCA) exerts multiple effects on pathways of intermediary metabolism. It stimulates peripheral glucose utilization and inhibits gluconeogeneis, thereby reducing hyperglycemia in animals and humans with diabetes mellitus. It inhibits lipogenesis and cholesterolgenesis, thereby decreasing circulating lipid and lipoprotein levels in short-term studies in patients with acquired or hereditary disorders of lipoprotein metabolism. By stimulating the activity of pyruvate dehydrogenase, DCA facilitates oxidation of lactate and decreases morbidity in acquired and congenital forms of lactic acidosis. The drug improves cardiac output and left ventricular mechanical efficiency under conditions of myocardial ischemia or failure, probably by facilitating myocardial metabolism of carbohydrate and lactate as opposed to fat. DCA may also enhance regional lactate removal and restoration of brain function in experimental states of cerebral ischemia. DCA appears to inhibit its own metabolism, which may influence the duration of its pharmacologic actions and lead to toxicity. DCA can cause a reversible peripheral neuropathy that may be related to thiamine deficiency and may be ameliorated or prevented with thiamine supplementation. Other toxic effects of DCA may be species-specific and reflect marked interspecies variation in pharmacokinetics. Despite its potential toxicity and limited clinical experience, DCA and its derivatives may prove to be useful in probing regulatory aspects of intermediary metabolism and in the acute or chronic treatment of several metabolic disorders.     

Usefulness of 2-dimensional echocardiography in detecting intraventricular thrombi in patients with acute myocardial infarction

The purpose of this study is to determine the importance of two-dimensional echocardiography performed soon after admission to the coronary care unit to provide useful information concerning wall-motion abnormalities, and to detect and characterize left ventricular thrombi. A major goal is to identify a subgroup of patients with acute myocardial infarction who are at risk for systemic embolization; in this subgroup the benefits of anticoagulation treatment would theoretically outweigh the associated risks. We studied 7 consecutive male patients, age range from 32 to 60 years, with acute myocardial infarction. Five patients had antero-septal infarction, 1 anterolateral and another had anterior wall infarction. We performed two-dimensional echocardiography within the first week after admission. All patients had severe apical-wall-motion abnormalities (akinesis or dyskinesis) and left ventricular thrombi. All patients received anticoagulation therapy. Two-dimensional echocardiography, performed one month after the first study, showed that the thrombi had decreased in size in 6 patients and could not be visualized in 1 patient. The noninvasive nature of echocardiography allows serial evaluations of patients with known left ventricular thrombi and permits assessment of the effect of therapy.     

Septal rupture repaired in the acute stage of myocardial infarction. Clinical, hemodynamic and angio-coronarography findings in the evaluation of surgical risk

Between 1977 and 1987, 27 consecutive patients (16 men, 11 women, mean age 66 years, range 54 to 75 years) with ventricular septal rupture complicating acute myocardial infarction underwent surgical repair. The purpose of this retrospective study was to analyse the post-operative mortality factors from clinical, haemodynamic and operative data in all patients and also from coronary angiographic data in 23/27 patients whose haemodynamic status allowed this type of exploration. Seventeen patients (63 p. 100) died during the first post-operative month, 10 survived and were discharged. Factors that influenced the prognosis were: (1) inferiorly-located necrosis associated with a 75 p. 100 mortality rate (9 out of 12 patients), as opposed to 53 p. 100 (8 out of 15 patients) with anterior necrosis; (2) right ventricular dysfunction, observed in 83 p. 100 of patients with inferior necrosis and 53 p. 100 with anterior necrosis, which was responsible for 7 out of 9 deaths in the inferior necrosis subgroup and contributed to 3 out of 8 deaths in the anterior necrosis subgroup; this established a cause-effect relationship between right ventricular function and the overmortality of patients with inferior necrosis; (3) independently of the haemodynamic status, two- and three-vessel lesions (56 p. 100 of all lesions) which had an 84 p. 100 mortality rate as opposed to 40 p. 100 with one-vessel lesions; (4) the presence of a state of shock which was associated with a 78 p. 100 mortality rate as opposed to 55 p. 100 in patients without shock. We conclude that when permitted by the patient's haemodynamic status coronary angiography should be part of the pre-operative evaluation to assess the operative risk and guide the surgical procedure.     

Enoximone and the therapeutic strategy in patients awaiting emergency cardiac graft

Enoximone is a positive inotropic agent belonging to the group of phosphodiesterase F-III inhibitors. The drug was tested in 34 patients uncontrolled by sympathomimetic drugs and referred to our department for urgent heart transplantation or circulatory assistance. After insertion of a Swan-Ganzgatheter and a radial artery catheter for haemodynamic monitoring, enoximone was administered as a 15-minute intravenous bolus injection of 1 to 2.5 mg/kf every 8 hours, in addition to sympathomimetic agents. Clinical and haemodynamic improvement was observed after thirty minutes in 30 patients. The cardiac index rose from 1.82 to 2.67 l/min/m2 and the pulmonary wedge pressure fell from 30.8 to 18.9 mmHg. Systemic arterial resistance decreased from 2170 to 1520 dyn. s. cm-5, and pulmonary resistance from 5.5 to 4.6 Wood units (p less than 0.01 for all values). Four patients had no haemodynamic improvement and were put on circulatory assistance, using a Jarvik 7 total artificial heart in 3 of them and heterotopic circulatory assistance in one. After clinical investigation for contra-indication to heart transplantation, and as their improved haemodynamic status permitted, 12 of the 30 patients were considered suitable (group B) for heart transplantation. Transplantation was performed within a week of admission in 11 patients without any need for mechanical assistance. One of the group B patients who required implantation of a Jarvik 7 artificial heart died after 12 hours of assistance. Eighteen patients were considered unsuitable for transplantation (group A) and treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)     

A central mechanism of acute baroreflex resetting in the conscious dog

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.     

C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.