Date of Award


Publication Type

Doctoral Thesis

Degree Name



Biological Sciences

First Advisor

Taylor, P. B.,


Biology, Animal Physiology.




Cardiac hypertrophy was induced by daily subcutaneous injections of isoproterenol (0.3 mg/kg. body weight) for 12 consecutive days. A significant increase in whole ventricular weight (35.7%) was achieved. Regionally, the right ventricle produced a greater hypertrophy response than the left ventricle. Contractile force, +Dt/dt, and $-$DT/dt in right ventricular trabecular muscle were significantly increased, suggesting that either Ca$\sp{2+}$ responsiveness of the myofilaments or the availability of (Ca$\sp{2+}\rbrack\rm\sb i$ was increased. The Ca$\sp{2+}$ sensitivity of the myofilaments was investigated using a Triton-100 skinned trabecular preparation. The force-pCa relationship showed no difference in the myofilament Ca$\sp{2+}$ sensitivity. The force-interval relationship was studied to reflect the early recovery of SR Ca$\sp{2+}$ release channels and the late diastolic Ca$\sp{2+}$ influx via sarcolemmal Na-Ca exchange. The SR Ca$\sp{2+}$ release characteristics were not altered, however, Ca$\sp{2+}$ influx via sarcolemmal Na-Ca exchange was enhanced in hypertrophied muscle. A biphasic rate staircase was found in trabecular muscle: negative from 0.1 to 0.5 Hz and positive from 0.5 to 2.5 Hz. Studies using rapid cooling contractures (RCCs) suggest that SR Ca$\sp{2+}$ content determines the amounts of SR Ca$\sp{2+}$ release. Ryanodine, which unloads SR Ca$\sp{2+},$ abolished the negative rate staircase. Nifedipine, $\rm I\sb{Ca}$ blocker, eliminated the positive response. These results suggest that diastolic SR Ca$\sp{2+}$ loading, probably via Na-Ca exchange, contributes to the negative phase, whereas Ca$\sp{2+}$ influx via L-type channel dominates the positive phase. In hypertrophied muscle ((Ca$\rm\sp{2+}\rbrack\sb o$ = 0.5 mM), the positive rate staircase was significantly enhanced, indicating an increased functioning of L-type Ca$\sp{2+}$ channel and a greater SR Ca content. There was a frequency-dependent prolongation of APD$\sb{50}$ and the APD$\sb{50}$ was significantly increased in hypertrophied muscle, suggesting that Ca$\sp{2+}$ influx, probably via $\rm I\sb{Ca},$ was increased with frequency and this pathway was significantly amplified in hypertrophied muscle. The capacity to remove cytoplasmic Ca$\sp{2+}$ was increased by either SR Ca-ATPase pump or sarcolemmal Na-Ca exchange in hypertrophied muscle. In summary, the increased (Ca$\rm\sp{2+}\rbrack\sb i$ handling pathways, such as $\rm I\sb{Ca},$ SR Ca$\sp{2+}$ content, Na-Ca exchange activity, and SR Ca-ATPase pump, contribute to the enhanced contractile function in hypertrophied muscle.Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1993 .T36. Source: Dissertation Abstracts International, Volume: 56-01, Section: B, page: 0116. Adviser: P. B. Taylor. Thesis (Ph.D.)--University of Windsor (Canada), 1993.