Protein kinase C mediates Ca2(+)-induced cardioadaptation to ischemia-reperfusion injury.

Although protein kinase C (PKC)-mediated cardioadaptation to ischemia-reperfusion (IR) is accompanied by increased intracellular Ca2+ concentration, it is unknown whether a preischemia sarcoplasmic reticulum (SR) Ca2+ release affects PKC-mediated post-IR functional protection. To study this, crystalloid-perfused (Langendorff) Sprague-Dawley rat hearts were used to assess the effects of a ryanodine (Ry)-induced preischemia Ca2+ load (Ry, 5 nM/2 min, retrograde coronary) 10 min before global IR (20 min). Ry was administered with and without each of two different PKC inhibitors (20 microM chelerythrine and 150 nM bisindolylmaleimide I-HCl).

Cardiac preconditioning with calcium: clinically accessible myocardial protection.

Cardiac preconditioning is mediated by protein kinase C. Although endogenous calcium is a potent stimulus of protein kinase C, it remains unknown whether preischemic administration of exogenous calcium can induce protein kinase C-mediated myocardial protection against ischemia-reperfusion injury. To study this, calcium chloride was administered retrogradely through the aorta at a rate 5 nmol/min for 2 minutes to isolated perfused rat hearts 10 minutes before a 20-minute ischemia and 40-minute reperfusion insult.

The obligate role of protein kinase C in mediating clinically accessible cardiac preconditioning.

Background: Cardiac preconditioning is an adaptation of cardiomyocytes that promotes tolerance to a subsequent ischemic insult. Adenosine receptor signaling is proposed as a mediator of preconditioning, but its mechanism of protection remains unknown. We hypothesized that protection against hypoxia-reoxygenation (H/R) injury could be conferred in a rat ventricle by adenosine-mediated protein kinase C (PKC) activation and that adenosine-mediated cardioprotection could be extended to human ventricular muscle.

Vinblastine attenuates endotoxin-induced impairment of CGMP-mediated pulmonary vasorelaxation.

We tested the hypothesis that neutrophils contribute to endotoxin-induced impairment of endothelium-dependent and -independent cyclic guanosine monophosphate (cGMP)-mediated pulmonary vascular smooth muscle relaxation. Rats were studied 6 h after endotoxin (20 mg/kg, intraperitoneal) or saline (1 cc, intraperitoneal). Neutrophil-depleted rats were studied 4 days after administration of vinblastine (750 micrograms/kg, intravenous).

Calcium-induced inotropy is in part mediated by protein kinase C.

Protein kinase C (PKC) is an ubiquitous regulatory enzyme with dense myocardial distribution and activity; however, its physiologic relevance to myocardial function remains poorly understood. Although endogenous Ca2+ is a potent stimulus of PKC isoforms alpha and beta (cPKCs) it remains unknown whether exogenous Ca2+ activates these PKC isoforms, and if so, whether PKC plays any role in Ca2+-induced myocardial inotropy. To study this, ventricular sections from isolated rat hearts, with and without Ca2+-induced inotropy (CaCl2, 0.

Ovarian stimulation for assisted reproduction.

Regimens for ovarian stimulation that result in increased circulating follicle-stimulating hormone with low levels of luteinizing hormone produce adequate follicular growth and improved oocyte quality and cycle outcome. Recombinant follicle-stimulating hormone for subcutaneous use and antagonists of gonadotropin-releasing hormone promise to simplify ovarian stimulation in the future.

Microtubules regulate pulmonary vascular smooth muscle contraction.

Microtubules are ubiquitous in eukaryotic cells. However, the role of microtubules in the mechanisms of pulmonary vascular smooth contraction has not previously been described. The purpose of this study was to examine the effect of microtubular inhibition (vinblastine) on the following mechanisms of pulmonary vascular smooth muscle contraction in rats using isolated pulmonary artery rings: (1) receptor-independent, calcium-dependent contraction via smooth muscle cell depolarization (response to KCl); (2) receptor-dependent, calcium-dependent contraction via alpha 1-adrenergic receptor stimulation (response to phenylephrine, PE); (3) receptor-dependent, calcium-independent contraction via thromboxane A2 receptor stimulation (response to the thromboxane mimetic, U-46619).

Cardiac surgical implications of calcium dyshomeostasis in the heart.

The prevalence of coronary artery disease renders myocardial ischemia a leading cause of morbidity and mortality. Both cardiac bypass operations and cardiac transplantation cause myocardial ischemia and reperfusion injury. Intracellular calcium transport and regulation are of paramount importance in both normal and pathologic myocardial states.

Antibody-mediated neutrophil depletion preserves pulmonary vasomotor function.

Neutrophil depletion is commonly used to examine the role of neutrophils in lung injury. However, the effect of neutrophil depletion per se on mechanisms of pulmonary vascular smooth muscle relaxation is unknown. The purpose of this study was to examine the effect of neutropenia on the following mechanisms of cGMP-mediated pulmonary vasorelaxation: (1) receptor-dependent endothelium-dependent relaxation (response to acetylcholine (ACh)), (2) receptor-independent endothelium-dependent relaxation (response to the calcium ionophore A23187), and (3) endothelium-independent relaxation (response to sodium nitroprusside (SNP)).

Cornual pregnancies in patients with prior salpingectomy undergoing in vitro fertilization and embryo transfer.

Objective: To examine the frequency of cornual pregnancy in patients with prior salpingectomy undergoing IVF.

Design: Review.

Setting: Private fertility practice.

Optimal myocardial preservation: cooling, cardioplegia, and conditioning.

Myocardial preservation techniques have evolved in conjunction with cardiac surgery and currently offer substantial protection against myocardial injury. We propose that cardiac preconditioning, a robust, endogenous mechanism of cardioprotection, is emerging as an important adjunct to current cardioplegic techniques. By reviewing the physiologic basis for current cardioplegic strategies, and understanding the cardioprotective benefits of preconditioning, we postulate that cardiac preconditioning may represent an important, clinically accessible component of myocardial protection.

Jack A. Barney Resident Research Award. Cardiopulmonary hazards of perihepatic packing for major liver injuries.

Background: Perihepatic packing has been shown to result in pathologic intra-abdominal hypertension. Although now recognized as impairing abdominal organ perfusion, the extent to which perihepatic packing affects cardiopulmonary function has not been elucidated.

Methods: We analyzed a 3-year experience with 11 patients who sustained major hepatic injuries requiring perihepatic packing to control hemorrhage.

Leuprolide acetate for inducing ovulation in women undergoing ovarian stimulation.

Objective: To determine whether leuprolide acetate (LA), given subcutaneously at the time of follicular maturity in stimulated cycles, can result in ovulation and in vivo fertilization.

Study Design: Sixty-seven women underwent 91 cycles of ovarian stimulation (OS) and received a single subcutaneous injection of 1 mg of LA when follicular maturity was reached. Only clomiphene citrate (CC) was used for 15 cycles, CC/FSH for 66 cycles and human menopausal gonadotropin only for 10 cycles.

Gonadotropin requirements of the developing follicle.

Objective: To evaluate follicular FSH and LH requirements during suppression of endogenous gonadotropins with the GnRH antagonist Nal-Glu and whether LH-like activity could be supplied by administering subcutaneous hCG.

Design: Randomized clinical trial.

Participants: Thirty-two normally cycling females in the late follicular phase (dominant follicle mean diameter > or = 14 mm).

The impact of constructional impairment on the WMS-R Visual Reproduction subtests.

The present study investigated the impact of constructional impairment on performance on the WMS-R Visual Reproduction subtests that measure memory for visual material. Thirteen subjects with constructional impairment had lower scores on the immediate and half-hour delayed Visual Reproduction subtests, relative to a cognitively comparable group of subjects without constructional impairment. However, the two groups did not differ with respect to their performance on the WMS-R Logical Memory subtests, which measure verbal memory.

Energetics of lymphocyte "burnout" in late sepsis: adjuvant treatment with ATP-MgCl2 improves energetics and decreases lethality.

Although it is known that decreased high-energy phosphates contribute to organ dysfunction following shock, it remains unknown whether changes in lymphocyte energetics contribute to the profound immune dysfunction that occurs in late septic shock. Moreover, while studies have shown that ATP-MgCl2 treatment after hemorrhagic shock improves tissue ATP levels and organ function, it remains unknown whether lymphocyte high-energy phosphates and immune functions are similarly affected by this agent after sepsis. To study this, sepsis was induced in C3H/HeN (endotoxin sensitive) mice by cecal ligation and puncture (CLP) and they were then treated intraperitoneally with ATP-MgCl2 or saline vehicle.

Successful pregnancies with unstimulated cycle oocyte donation using an antagonist of gonadotropin-releasing hormone.

We achieved two ongoing pregnancies in five older recipients with natural cycle oocyte donation from five young donors using a GnRH antagonist, with hMG and hCG to complete oocyte maturation. This provides a new alternative to ovarian stimulation for both oocyte donation and routine IVF.

Cardiac preconditioning. Induction of endogenous tolerance to ischemia-reperfusion injury.

Cardiac preconditioning is a phenomenon by which a brief exposure to ischemia renders the heart more tolerant of a subsequent sustained ischemic insult. Understanding the mechanism involved may allow pharmacologic access to this protective state before cardiopulmonary bypass surgery and transplantation. We discuss herein the preconditioning phenomenon, the potential mechanisms involved, and the therapeutic implications of cardiac preconditioning.

Mechanism of diltiazem's immunomodulatory effects after hemorrhage and resuscitation.

Although diltiazem improves immune responses after hemorrhage and resuscitation, its mechanism remains unknown. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mmHg, maintained at that level for 1 h, and then adequately resuscitated and treated with diltiazem (400 micrograms/kg body wt) or saline (vehicle). One hour after hemorrhage and resuscitation, splenic microvascular blood flow was determined by laser Doppler flowmetry.

The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression.

Haemorrhage in the absence of trauma is reported to induce a profound depression in cell-mediated immunity. Recent studies have drawn attention to the cytokine transforming growth factor-beta (TGF-beta) that, while important in wound healing, also has marked immunosuppressive effects. The aim of this study was to determine whether: (1) haemorrhage induces an increase in circulating TGF-beta and if this is associated with the loss of host immunoresponsiveness; and (2) administration of monoclonal antibody (mAb) to TGF-beta following haemorrhage ablates these changes.

Female reproductive aging--ovarian and uterine factors.

Objectives: To review published data on ovarian and uterine aging in the human female.

Data Identification: Literature review.

Study Selection: Studies examining the effect of age on oocyte quality and uterine receptivity.