Effects of chlorpromazine as a systemic vasodilator during cardiopulmonary bypass in neonates

OBJECTIVES: Vasodilator use during cardiopulmonary bypass is important in pediatric cardiac surgery, but the full range of their effects on hemodynamics remains to be clarified. We studied the effects of chlorpromazine, a potent alpha-blocking agent, in neonates. METHODS: Subjects were 60 neonates undergoing arterial switch operations for complete transposition of the great arteries with an intact ventricular septum. Of these, 37 received 2.1 to 6.5 mg/kg of chlorpromazine during cardiopulmonary bypass (CPZ group) and 23 received no vasodilator (control group). We then compared hemodynamic parameters between groups during and early after surgery. RESULTS: The systemic vascular resistance index and mean arterial pressure during cardiopulmonary bypass were significantly lower in the CPZ group (p < 0.05), but systolic pressure 15 minutes after cessation of cardiopulmonary bypass did not differ between groups. The rise in peripheral temperature during rewarming after hypothermia was significantly higher and the acid-base status 40 minutes after cardiopulmonary bypass less acidotic in the CPZ group. Urine output during cardiopulmonary bypass was higher in the CPZ group. CONCLUSIONS: Chlorpromazine effectively counteracts systemic vasoconstriction induced by cardiopulmonary bypass without serious side effects in neonatal cardiac surgery.     

Surgical repair of total anomalous pulmonary venous connection in neonates and infants--prevention for pulmonary venous obstruction at the site of anastomosis

From October, 1980, to June, 1987, thirty-eight infants less than one year old underwent correction for total anomalous pulmonary venous connection (TAPVC). Overall operative mortality and late mortality were 13% and 6%, respectively. Residual pulmonary hypertension was noted in 4 patients: three had pulmonary venous obstruction at the site of atrial anastomosis (PVOA) and one had supracardiac (Ia) lesion left after repair of mixed type (IV: Ia + III) of TAPVC. Two late deaths occurred in these with PVOA. Twenty-two patients with supracardiac (I) or infracardiac (III) TAPVC were divided into three groups according to the technical development in atrial anastomosis: the large anastomosis in which venous incision reached into at least one pulmonary vein beyond common pulmonary vein and the continuous running suture were used in 10 patients (group 1), the appropriate size of anastomosis in which venous incision limited within the common pulmonary vein and the continuous running suture used in 4 patients (group 2), and the appropriate size of anastomosis and the interrupted suture in 8 patients (group 3). PVOA were 3 (33%) in group 1, but 0 (0%) in group 2 and 3. Two late death occurred all in group 1 with PVOA. Cardiopulmonary bypass time and aortic clamp time in group 3 were 91 min and 74 min respectively, which did not become longer than those in both group 1 and group 2. Interrupted suture technique does not make operating time longer than continuous running suture one. PVOA is one of the important factors predicting late operative result.(ABSTRACT TRUNCATED AT 250 WORDS)     

Movement of the lateral and medial poles of the working condyle during mastication in patients with unilateral posterior crossbite.

Patients with unilateral posterior crossbite often show reverse sequential jaw movement patterns on the frontal view during mastication on the crossbite side. Recent studies show that such patients are prone to suffer from temporomandibular joint (TMJ) disc displacement, particularly the lateral portion. The purpose of this study was to examine the movement of the lateral and medial poles of the working condyle during mastication in such patients. Subjects were 12 consecutive patients with unilateral posterior crossbites and without TMJ disc displacements and 12 normal subjects. An optoelectronic jaw-tracking system with 6 degrees of freedom was used to record the motion of the lateral and medial poles of the working condyle during mastication of standardized hard, gummy jelly. The data from the first 10 cycles were analyzed. The lateral and medial poles of the condyle on the crossbite side moved more in the medial direction and less in the lateral direction during mastication in the crossbite patients than the condyle in the normal subjects. The lateral pole of the working condyle moved more in the posterior and inferior directions and less in the anterior direction than the medial pole in all subjects. These results suggest that these condylar movements in patients with unilateral posterior crossbites might be related to the susceptibility to TMJ disc displacement, particularly the lateral portion.     

Metalloproteinase activity is present in rat urine and derived from the renal cortex

Summary: Matrix metalloproteinases (MP) are important candidates for the degradation of extracellular matrix, but the role of MP in the diseased kidney remains poorly understood. to examine the significance of urinary MP, we first investigated the characteristics of MP in normal rat urine and renal cortex, and then evaluated the urinary MP activity in anti-thymocyte induced glomerulonephritis (Thy.1 GN). Metalloproteinase activity was measured as the EDTA-inhibitable degradation of [³H] gelatin. the enzyme was purified from urine and the renal cortex homogenate in normal Wistar rats by using several chromatographic and gel filtration methods. Both materials contained the identical molecular weight (Mr 126 kDa by gel permeation method) of gelatin-degrading enzymes, the activity of which was inhibited by metal chelating agents and reactivated by ZnC1₂ but not by other proteinase inhibitors. Thy.1 GN was induced by intravenous injection of rabbit anti-thymocyte serum into rats, and daily urine was collected at sequential time points. Urinary MP activity was markedly reduced soon after the serum injection, and returned to the control level in 9 weeks. Conversely, urinary MP-inhibitor activity (Mr 30 kDa), determined as inhibiting activity against MP derived from renal cortex, showed serial changes strikingly reflected as urinary MP activity. These findings suggested that rat urine contained the MP which seemed to be derived from the renal cortex, and the urinary MP activity was decreased in Thy.1 GN model, probably due to the presence of MP-inhibitor. As urinary MP is likely to reflect intra-renal MP, the evaluation of urinary MP may be useful to search metabolic alteration of extracellular matrix in the diseased kidney.     

Relationships between the serum levels of soluble leptin receptor and free and bound leptin in non-pregnant women of reproductive age and women undergoing controlled ovarian hyperstimulation

BACKGROUND: The aim of this study was to investigate the relationships between the serum levels of soluble leptin receptor (SLEPR), and total, free and bound leptin, and the change in the serum SLEPR level during an IVF cycle. METHODS: Serum concentrations of leptin and SLEPR were measured in 50 Japanese women of reproductive age, and 20 patients participating in an IVF programme. The total leptin was fractionated into free and bound portions by gel filtration chromatography. RESULTS: The SLEPR level was negatively correlated with the body mass index (BMI) (r = -0.548, P < 0.0001), total leptin (r = -0.433, P < 0.0001), the percentage of free leptin (r = -0.732, P < 0.0001) and the absolute free leptin concentration (r = -0.506, P < 0.0001). The SLEPR level was positively correlated with the percentage of bound leptin (r = 0.730, P < 0.0001), whereas there was little variation in the absolute bound leptin concentration, regardless of the BMI or SLEPR concentration. During the IVF cycle, total and free leptin elevated during maximal ovarian stimulation, whereas there was no significant difference in the SLEPR concentration. CONCLUSIONS: The results demonstrate a skillful mechanism where a change in the serum SLEPR level regulates, in part, the biological activity of leptin in the circulation.     

Hyperpolarizing current of the Na/K ATPase contributes to the membrane polarization of the Purkinje cell in rat cerebellum

 The contribution of the Na/K ATPase (pump) current to the polarization of the Purkinje cell has been studied using slices of the rat cerebellum by blocking the pump with dihydro-ouabain (DHO) while recording the membrane potential with microelectrodes in the somata. From our recordings, it appeared that blocking the pump depolarized the Purkinje cells more rapidly than might be expected from shifts in Na⁺ and K⁺ concentrations, suggesting the removal of a hyperpolarizing current. Application of DHO, in the presence of tetrodotoxin (TTX), led to calcium spike firing and plateau-like discharges suggesting activation of voltage-dependent calcium channels in the dendrites. Adding 2 mM Co²⁺ to the medium did not prevent the depolarizations. Removing calcium from the bathing medium containing 2 mM Co²⁺ blocked the spiking activity but DHO application still produced a depolarization. Experiments to measure the current inhibited by DHO indicated that the Na/K pump supplies a constant current of 240 pA. Substitution of the sodium with choline produced a hyperpolarization, during which DHO had no effect on the membrane potential. Substitution of the sodium with lithium produced only a slowly developing depolarization. It is concluded that in the cerebellar Purkinje cell, a continuous sodium ion influx activates the pumps which produce a current that directly contributes to the membrane polarization. Possible pathways for this sodium influx are discussed. Received: 3 April 1997 / Received after revision and accepted: 12 May 1997     

Mixed connective tissue disease with fatal pulmonary hypertension and a review of literature

Summary The paper presents an autopsy case of mixed connective tissue disease (MCTD) with pulmonary hypertension (PH) and a review of literature. A 33-year-old woman with Raynaud's phenomenon and dyspnea of one year duration was diagnosed as having MCTD on the basis of a higher titer (1:163,840) of serum antibodies to the ribonucleoprotein (RNP). Cardiac catheterization showed complicating PH, confirmed an autopsy by the findings of concentric intimal cellular proliferation and typical plexiform lesions in the small arteries and arterioles of the lung, suggesting primary PH. Fatal PH with MCTD has been reported only 6 cases in literature including our case. All were young females, with histopathological findings consistent with plexogenic pulmonary arteriopathy in 5 cases and with recurrent pulmonary thromboembolism in the other. The aetiology of PH is still unknown, but it may be due to vasoconstriction evoked by the hyper-reactivity of the vessels.     

Histopathological studies of microtubule disassembling agent-induced myocardial lesions in rats

Microtubule disassembling agents (MDAs) such as colchicine (COL) and vincristine sulfate (VCR) are known to be cardiotoxic. However, few attempts have been made to histopathologically examine cardiac lesions induced by MDAs. In this study, we endeavored to induce myocardial injury in rats by administering MDAs and to clarify the morphological features of these myocardial lesions. Male rats were intravenously administered COL (1.00 or 1.25 mg/kg for 2 days at single daily doses) or VCR (0.50 or 0.75 mg/kg for 2 days at single daily doses). The day after administration, hearts were excised and examined histopathologically, immunohistochemically and electron microscopically. Degeneration and necrosis of myocardial cells with vacuolation were observed in rats administered COL at 1.25 mg/kg or VCR at 0.75 mg/kg. Electron microscopic examination revealed vacuoles in swollen mitochondria. Moreover, there were cells showing pyknosis and karyorrhexis in the interstitium. TUNEL and immunohistochemical staining for endothelial cells and electron microscopic examination identified the apoptotic cells in the interstitium to be vascular endothelial cells. These vascular endothelial lesions were induced by lower doses of MDAs than were myocardial lesions. Furthermore, common sites of cardiac lesions induced by MDAs had almost the same distribution as areas positive for pimonidazole, a marker of hypoxia. These findings indicate that MDAs occasionally damage mitochondria in myocardial cells, and suggest that these changes involve microcirculatory dysfunction induced by endothelial cell injury.     

Temporal stability of urinary cadmium in samples collected several years apart in a population of older persons

Objectives

There is growing evidence that urine cadmium is a temporally stable biomarker indicative of long-term cadmium exposure; however questions remain with regard to generalizability to older persons, the impact of changes in smoking behavior, and the degree of temporal stability when repeat sample collection spans years instead of weeks or months.