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Biomedical subjects

R C Tan

Publications and source records attributed to R C Tan.

28 records · Page 2Linked to original sources
PubMed1989

Modulation of the Purkinje-ventricular muscle junctional conduction by elevated potassium and hypoxia.

Action potential transmission in the canine ventricle normally occurs from the Purkinje (P) system into the ventricular muscle (VM) at specific P-VM junction sites. Transitional (T) cells are located between the Purkinje and the ventricular (V) cells at these P-VM junction sites. It has been shown that exposure to elevated [K+]0 in combination with hypoxia produces an increase in the P-VM conduction time. To examine this increase in P-VM conduction time, simultaneous measurements of the action potential upstrokes of T cells and the activation times of the local P and V cells at P-VM junctional sites were obtained from in vitro canine papillary muscles. The effects of elevated [K+]0 and hypoxia on conduction from P cells to T cells was then compared with the conduction from T cells to V cells to assess the relative contribution of each to the increase in the P-VM conduction time. We found that this intervention has approximately equal effects on the two sequential steps involved in P-VM conduction. We then analyzed the increased delay from T cells and V cells on the basis of three hypothetical mechanisms: 1) increased coupling resistance, 2) decreased V cell excitability, and 3) decreased cellular responsiveness of the T cells. Our results show that the effects of elevated [K+]0 and hypoxia on T-VM delay can be accounted for by a decreased responsiveness of the T cells without any significant electrical uncoupling between T and V cells or decrease in VM excitability.

Action Potentials↗
PubMed1989

Developmental changes in the electrophysiologic properties of rabbit papillary muscles.

We studied the electrophysiological properties of adult (AD) and newborn (NB) rabbit papillary muscles in vitro with superfusion of normal Tyrode's solution, solutions with elevated [K+]o, and in solutions with various concentrations of tetrodotoxin. In control solutions, the NB papillary muscles had a more negative resting membrane potential (-83.6 +/- 1.2 versus -80.0 +/- 1.5 mV), a higher rate of rise of phase 0 (134 +/- 5 versus 120 +/- 5 V/S) and a higher, longer-lasting action potential plateau than the AD papillary muscles. Exposure to elevated [K+]o led to a significant post-repolarization refractoriness in AD papillary muscles that was more than that for NB papillary muscles even when NB papillary muscles were depolarized to the same resting membrane potential as the AD papillary muscles. The NB papillary muscles were comparatively resistant to tetrodotoxin in terms of percent reduction of conduction velocity and percent rise in the current threshold for excitation. The conduction velocity for AD papillary muscles in control solution (66 +/- 6 cm/s) was more than for NB papillary muscles (44 +/- 4 cm/s), which would not be expected from the data on the rate of rise of the action potential, suggesting that the cable properties of NB papillary muscles (specifically a greater surface to volume ratio of the ventricular cells) are also significantly different from the AD papillary muscles.

Action Potentials↗
PubMed1987

Adenosine and hypoxia effects on atrioventricular node of adult and neonatal rabbit hearts.

An isolated perfused heart model was used to assess the effects of hypoxia and adenosine on the adult and neonatal (1-5 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by the A-H interval at a constant atrial pacing cycle length and by the longest pacing cycle length resulting in Wenckebach periodicity. We defined the pacing cycle length at or below which the AV node demonstrated Wenckebach periodicity as the Wenckebach cycle length. Adenosine produced a smaller dose-dependent increase in A-H interval in neonates than in adults, but the increase in Wenckebach cycle length was similar in the two age groups. When the hearts were exposed to 5 min of hypoxia the increase of Wenckebach cycle length was greater for adults than for neonates. The change in Wenckebach cycle length in adults caused by hypoxia was significantly greater than that caused by 1 mM adenosine. In addition, in adults aminophylline could partially attenuate the increase in Wenckebach periodicity caused by adenosine, but aminophylline could not attenuate the increase in Wenckebach cycle length caused by hypoxia. We conclude that in the rabbit AV node 1) the adenosine effect in neonates is similar to that in adults; 2) neonates are relatively resistant to acute hypoxia compared with adults; and 3) the response to acute hypoxia in adults cannot be totally explained by the adenosine release theory.

Adenosine↗
PubMed1987

Alterations in endocardial activation of the canine papillary muscle early and late after myocardial infarction.

Permanent coronary occlusion produces time-dependent changes in surviving subendocardial cellular properties. We compared the functional alterations in Purkinje (P) and ventricular muscle (VM) activation early (24 hr) and late (4 weeks or greater) after permanent coronary occlusion in an in vitro preparation of canine papillary muscle. High-density extracellular (1 to 2 mm resolution) and selected intracellular recordings were made in five animals early and seven animals late during stimulation of a free-running P strand. Activation patterns of P and VM layers from ischemic and unaffected papillary muscles were compared in the same animal. Average P layer conduction velocity was determined in normal and ischemic regions with the use of a linear array of recording and stimulating electrodes. Purkinje activation was altered little in the early phase of infarction, while healing was associated with a generalized 25% reduction in P layer conduction velocity and localized block and fragmentation of P waveforms. Intracellular recordings at sites of nonsynchronous P activation revealed electrotonic interaction between cell groups. At 24 hr, small groups of VM were present but with abnormal activation patterns in regions of necrosis with fragmented and delayed extracellular waveforms produced by partially uncoupled groups of cells. Local delay and block could be modulated by rate and site of stimulation. After healing, VM activation abruptly stopped at the visual infarct border, marked by a characteristic "end potential." These studies demonstrate important differences in the functional attributes of the P and VM layers studied early and late after coronary occlusion. Alterations in cell-to-cell relationships are likely very important in determining abnormalities of activation in both settings.

Animals↗
PubMed1987

Effects of hypoxia, hyperkalemia, and metabolic acidosis on canine subendocardial action potential conduction.

We have studied the individual and combined effects of elevated external potassium concentration (8 mM [K+], metabolic acidosis (pH = 6.8), and hypoxia at different stimulation 400 milliseconds) on Purkinje (P) and ventricular (V) conduction velocities and on Purkinje-ventricular junctional conduction delay (PVJ delay) in in vitro preparations from canine ventricles. Elevated [K+] had opposite effects on P and V velocities, increasing V velocity by 8% while reducing P velocity by 7%. Acidosis reduced P velocity by 9% while reducing V velocity by only 4%. Hypoxia and rapid stimulation rates had no significant effect on either P or V velocities. All test solutions (except hypoxia alone) significantly increased the PVJ delay. The magnitude of the increase in PVJ delay was much greater than the effects on either P or V velocity. In addition, hypoxia and rapid stimulation augmented the increase in PVJ delay in the presence of elevated [K+] and/or acidosis. The special features of conduction at the PV junctional sites may produce altered pathways of excitation of the ventricles during myocardial ischemia.

Acidosis↗
PubMedDate not supplied

Altered testosterone feedback in pubertal male rats raised on reduced caloric intake.

A study was conducted to explore the hypothesis that reduced caloric intake increases the negative feedback efficacy of testosterone on gonadotropin secretion. Daily subcutaneous injections of testosterone propionate in oil were administered to either age-matched (37-day-old) or weight-matched (mean = 178 g) ad libitum-fed (control) or underfed rats that received 60% of normal daily food intake from the age of 20 days. Daily doses of testosterone propionate ranged from 25 to 400 micrograms/100 g body weight. Results indicate that reduced caloric intake increases the suppression of serum LH by testosterone propionate in both age-matched and weight-matched underfed rats. On the other hand, the response of serum FSH concentrations to testosterone propionate was affected by reduced diet only in the weight-matched animals. Results suggest that the increased negative feedback of testosterone on LH secretion is a specific diet-induced effect and not merely the result of reduced growth. The altered response in FSH secretion, however, may represent age-associated changes in sensitivity to testosterone rather than diet-induced effects.

Animals↗
PubMedDate not supplied

In vitro infection of primate PBMC with simian/human immunodeficiency virus, SHIV(SF33A): correlation to in vivo outcome.

The macaque/SIV animal system is an important model for studying AIDS pathogenesis and for evaluating the efficacy of vaccines and anti-viral therapeutics. However, differences between HIV-1 and SIV envelope proteins exist that render the SIV/macaque model of limited value when examining envelope determinants of retroviral pathogenesis. To overcome this problem, we utilized a chimeric virus, SHIV(SF33), containing the env gene from HIV-1SF33 in the context of the molecular clone SIVmac239, in the macaque animal model. In this study SHIV(SF33A), a pathogenic virus that evolved in vivo from a rhesus macaque infected intravenously with the molecular clone SHIV(SF33) was used in both in vitro and in vivo studies. By using a cell culture system, we examined the biological properties of our parental and animal-adapted chimeric viruses and compared in vitro susceptibility to in vivo studies.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

In vivo adaptation of SHIV(SF162): chimeric virus expressing a NSI, CCR5-specific envelope protein.

The chemokine receptor CCR5 is known to be a critical determinant of human immunodeficiency virus (HIV) transmission and pathogenesis in the human host. Towards the development of a macaque model to evaluate the efficacy of vaccines and therapeutics against infection with CCR5-specific viruses, and to delineate the pathogenic properties of such viruses, we constructed a chimeric simian human immunodeficiency virus, SHIV(SF162), containing the env, tat, rev, and vpu genes from HIV-1(SF162) (R5, MT/NSI) in the context of the molecular clone simian immunodeficiency virus, SIV(mac239). Virus generated from this molecular clone was used to intravenously infect two juvenile macaques, followed by three consecutive serial blood/bone marrow transfusions. Animals infected with parental SHIV(SF162) (P1) had detectable levels of viral replication (as determined by p27(gag) production) within days of infection; however, viral set-points fell below detection by Week 3. Late passage animals (P3 and P4) had a two-log increase in the level of plasma p27(gag) antigen. These results demonstrate that in vivo serial passage of the R5-specific SHIV(SF162) enhanced its replicative capacity.

AIDS Vaccines↗