PubMed Health⌕ Search

Biomedical subjects

T A McKean

Publications and source records attributed to T A McKean.

17 recordsLinked to original sources
PubMed2001

Calcium transport mechanisms in muskrat and rat hearts.

Mammalian hearts experience calcium overload during extreme and prolonged hypoxia and the calcium overload may lead to enzyme activation and cell death. Several calcium transport systems were examined in muskrat hearts and compared to those found in rat hearts to determine if there is a species difference that might be related to the muskrats' superior ability to survive hypoxia. Radiolabeled nitredendipine binding was determined in rat and muskrat hearts to estimate the density of voltage gated calcium channels in surface membranes. There were no species differences. Calcium release channel density in the sarcoplasmic reticulum was estimated by the determination of radiolabeled ryanodine binding in muskrat and rat heart SR membranes. No differences were revealed between species. The SR uptake of calcium was measured in SR membranes from the hearts of the two species. No differences were found in the B(max) values, however, the muskrat SR membranes did have a slightly lower K(m) value. There were large species differences in Na(+)/Ca(2+) exchange in SL membranes with the muskrat heart having approximately 3.5 times the transport capacity of rat SL membranes. During hypoxic conditions in which there is extensive ATP depletion leading to [Na(+)](i) accumulation and discharge of cellular membrane potential, the Na(+)/Ca(2+) exchanger may operate in the reverse mode and import calcium into the cell and accelerate hypoxic damage. Prior to reaching this state a robust Na(+)/Ca(2+) exchange would facilitate the maintenance of normal diastolic calcium levels and calcium cycling. Muskrats hearts are hypoxia tolerant by virtue of their ability to reduce metabolic demand and generate ATP anaerobically thus, maintaining a favorable ATP balance. Therefore, the relative overexpression of Na(+)/Ca(2+) exchangers in muskrat hearts may be beneficial in the preservation of contractile function and calcium homeostasis in this freshwater diving mammal.

Adenosine Triphosphate↗
PubMed1994

The effect of ATP-sensitive potassium channel modulation on heart rate in isolated muskrat and guinea pig hearts.

Muskrats (Ondontra zibethicus) are common freshwater diving mammals exhibiting a bradycardia with both forced and voluntary diving. This bradycardia is mediated by vagal innervation; however, if hypoxia is present there may be local factors that also decrease heart rate. Some of these local factors may include ATP-sensitive potassium channel activation and extracellular accumulation of potassium ions, hydrogen ions and lactate. The purpose of this study was to investigate the role of these factors in the isolated perfused hearts of muskrats and of a non-diving mammal, the guinea pig. Although lactate and proton administration reduced heart rate in isolated muskrat and guinea pig hearts, there was no difference in the response to lactate and proton infusion between the two species. Muskrat hearts were more sensitive to the heart-rate-lowering effects of exogenously applied potassium than were guinea pig hearts. Early increases in extracellular potassium concentration during hypoxia are thought to be mediated by the ATP-sensitive potassium channel. Activation of these channels under normoxic conditions had a mildly negative chronotropic effect in both species; however, activation of these channels with Lemakalim under hypoxic conditions caused the guinea pig heart to respond with an augmented bradycardia similar to that seen in the hypoxic muskrat heart in the absence of drugs. Inhibition of these channels by glibenclamide during hypoxia was partially successful in blocking the bradycardia in guinea pig hearts, but inhibition of the same channels in hypoxic muskrat hearts had a damaging effect as two of five hearts went into contracture during the hypoxia. Thus, although ATP-sensitive potassium channels appear to have a major role in the bradycardia of hypoxia in guinea pigs, the failure to prevent the bradycardia by inhibition of these channels in muskrat hearts suggests that multiple factors are involved in the hypoxia-induced bradycardia in this species.

Adenosine Triphosphate↗
PubMed1993

Effect of adenosine on heart rate in isolated muskrat and guinea pig hearts.

The purpose of this study was to compare the responses of isolated hearts of the diving muskrat with the nondividing guinea pig (GP) to determine the contribution of adenosine (ADO) to the profound bradycardia that was seen in isolated muskrat hearts during exposure to hypoxia. Muskrat hearts were more sensitive than GP hearts to the heart rate-lowering effects of exogenously applied ADO or a stable ADO analogue, (R)-N6-(phenylisopropyl)adenosine. The hearts of both species were unpaced, and the bradycardia appeared to be due to high degree of atrioventricular block. Radioligand binding with 8-cyclopentyl-1,3-[3H]dipropylxanthine to A1-ADO receptors was greater in cardiac membranes prepared from GP hearts than from muskrat hearts. Nucleoside transporter antagonist binding was also greater in GP hearts compared with muskrats. This was determined by membrane binding of [3H]-nitrobenzylthioinosine, an antagonist of nucleoside transport. Both muskrat and GP hearts responded to 30 min of hypoxic perfusion by releasing ADO into the coronary effluent; however, the muskrat hearts released approximately five times more than the GP hearts. When hearts were subjected to hypoxia in the presence of ADO deaminase, theophylline, or 8-(p-sulfophenyl)theophylline, the hypoxia-induced bradycardia was blocked in the GP hearts and either slightly reduced or not affected in muskrat hearts. In contrast to GP hearts, muskrat hearts release larger amounts of ADO during hypoxia and are more sensitive to the negative chronotropic effects of exogenously administered ADO; yet the hypoxia-induced bradycardia does not appear to be exclusively mediated by ADO in the muskrat as it is in the isolated GP heart.

Adenosine↗
PubMed1992

Influence of ATP-sensitive potassium channel blocker on hypoxia-induced damage of isolated guinea pig heart.

1. Isolated guinea pig hearts were perfused under constant flow conditions with Krebs-Henseleit buffer. Hearts were subjected to 15 min of hypoxia followed by reoxygenation in the presence and in the absence of 100 microns glyburide, an ATP-sensitive potassium channel blocker. Heart rate, left ventricular pressure and lactate dehydrogenase (LDH) release were measured at 5 min intervals. 2. Small decreases in heart rate and left ventricular pressure were observed during glyburide infusion with hypoxia, however LDH release, which was used as an index of cellular damage, was dramatically elevated. 3. Neither glyburide, nor the vehicle in which it was dissolved, appeared to produce myocardial damage under normoxic conditions. 4. It is concluded that ATP-sensitive potassium channels are important in the protection of the myocardium during hypoxia in isolated guinea pig hearts perfused under constant flow conditions.

Adenosine Triphosphate↗
PubMed1991

Calcium uptake by mitochondria isolated from muskrat and guinea pig hearts.

Subsarcolemmal and interfibrillar mitochondria were isolated from the hearts of the diving muskrat and non-diving guinea pig and direct and indirect measurements of calcium uptake were examined in vitro. The calcium-stimulated respiration rate and 45Ca uptake were measured and found to be greater in muskrat than in guinea pig mitochondria. Muskrat mitochondria were able to endure a greater external calcium concentration than guinea pig mitochondria before exhibiting indications of inner membrane damage. Calcium uptake by muskrat heart mitochondria was inhibited more by 1 mmoll-1 MgCl2 than was uptake by guinea pig mitochondria. No differences were detected between the interfibrillar and subsarcolemmal populations of mitochondria within species. An increased ability to sequester calcium by mitochondria without causing them damage may aid an animal during recovery from hypoxia, ischemia or acidosis.

Animals↗
PubMed1990

Comparison of respiration in rat, guinea pig and muskrat heart mitochondria.

1. Subsarcolemmal and interfibrillar mitochondria were isolated from the hearts of the diving muskrat and non-diving guinea pig and rat. Respiration rates, respiratory control ratio (RCR) and phosphorous to oxygen (P:O) ratios determined. 2. There was no significant difference in these values among the three species or between mitochondrial populations. 3. Mitochondrial yield as measured by citrate synthase of whole heart homogenates was greatest in the rat, intermediate in the muskrat and lowest in the guinea pig. 4. Muskrat heart mitochondria do not differ from rat and guinea pig heart mitochondria in the ability to use pyruvate as a substrate. 5. Differences in heart mitochondrial function between diving and non-diving rodents were not found and thus do not appear to be adaptations for the hypoxia of diving.

Animals↗
PubMed1988

The density of beta-adrenoreceptors in cardiac muscle membranes of muskrats and guinea pigs.

1. Cardiac membranes were prepared and then incubated with a range of concentrations of the beta-adrenergic ligand, dihydroalprenolol. Specific binding to the receptor was measured and receptor density and binding affinities were determined. 2. The receptor density was about 40% greater in the guinea pig heart than in the muskrat heart. The reduced beta-receptor density in the muskrat heart helps explain the previous findings of a lesser pumping ability and decreased responsiveness to isoproterenol in the muskrat compared with guinea pig hearts. 3. The decreased beta-receptor density may aid the muskrat in diving by reducing the oxygen consumption of the heart and thus prolonging diving time.

Animals↗
PubMed1987

Glucose oxidation and oxygen consumption of isolated guinea pig and muskrat hearts.

Glucose in Krebs-Henseleit buffer was presented to isolated Langendorff perfused muskrat and guinea pig hearts that were paced at 240 beats/min. Glucose uptake (amount removed from the perfusion fluid) was 3 times greater in the muskrat hearts than in the guinea pig heart. Glucose oxidation (amount converted to CO2) and oxygen consumption did not differ in the hearts of the two species. When glucose is the only exogenous substrate, isolated muskrat hearts extract more glucose than guinea pig hearts but oxidize similar amounts of glucose and have a similar myocardial oxygen consumption.

Animals↗
PubMed1984

Effect of exercise on uterine blood flow in the pregnant Pygmy goat.

Pygmy goats in the last third of pregnancy were trained to walk on a treadmill at rates up to 2.0 mph and up an inclination of 0-15 degrees. Electromagnetic flowmeters were placed unilaterally on a uterine artery, and measurements were made while the goats were standing quietly on the treadmill and during 5 min of exercise. Blood flow fell during exercise in all five animals studied, and this reduction was proportional to the level of exertion. At the highest level of exercise that these animals would voluntarily perform, uterine artery blood flow fell by 32 +/- 3 (SE) % (P less than 0.001) from control. In four additional animals the radioactive microsphere technique was used to measure uterine blood flow at rest and after 5-7 min of exercise. In these animals, exercise caused total uterine blood flow to fall by 18 +/- 10%; cotyledonary (placental) blood flow fell by 8 +/- 13%, while myoendometrial blood flow decreased by 52 +/- 12% (P less than 0.05). Thus nonplacental portions of the pregnant Pygmy goat uterus suffer major reductions in blood flow during exercise. This vasoconstriction may be due to exercise per se or to concomitant hypocapnia or hyperthermia. Singleton and twin kids born to animals that exercised were of normal birth weight.

Animals↗