Abstract
Background: The present study was performed to test the hypothesis that the altered force-frequency relation in human failing dilated cardiomyopathy may be attributed to alterations in intracellular calcium handling. Methods and Results: The force-frequency relation was investigated in isometrically contracting ventricular muscle strip preparations from 5 nonfailing human hearts and 7 hearts with end-stage failing dilated cardiomyopathy. Intracellular calcium cycling was measured simultaneously by use of the bioluminescent photoprotein aequorin. Stimulation frequency was increased stepwise from 15 to 180 beats per minute (37°C). In nonfailing myocardium, twitch tension and aequorin light emission rose with increasing rates of stimulation. Maximum average twitch tension was reached at 150 min-1 and was increased to 212±34% (P<.05) of the value at 15 min-1. Aequorin light emission was lowest at 15 min-1 and was maximally increased at 180 min-1 to 218±39% (P<.01). In the failing myocardium, average isometric tension was maximum at 60 min-1 (106±7% of the basal value at 15 min-1, P=NS) and then decreased continuously to 62±9% of the basal value at 180 min-1 (P<.002). In the failing myocardium, aequorin light emission was highest at 15 min-1. At 180 min-1, it was decreased to 71±7% of the basal value (P<.01). Including both failing and nonfailing myocardium, there was a close correlation between the frequencies at which aequorin light emission and isometric tension were maximum (r=.92; n=19; P<.001). Action potential duration decreased similarly with increasing stimulation frequencies in nonfailing and end-stage failing myocardium. Sarcoplasmic reticulum 45Ca2+ uptake, measured in homogenates from the same hearts, was significantly reduced in failing myocardium (3.60±0.51 versus 1.94±0.18 (nmol/L) · min-1 · mg protein-1, P<.005). Conclusions: These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1169-1178 |
| Number of pages | 10 |
| Journal | Circulation |
| Volume | 92 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 1 1995 |
| Externally published | Yes |
Bibliographical note
Funding Information:Chile has a long tradition of mixed public and private involvement in the health of the population. The country’s first sanitary law establishing public responsibility for sanitation and preventive health was issued in 1918. In 1924, a general social insurance scheme that included sickness coverage for blue collar workers was organized; this arrangement was revised in 1938 to include preventive health services. By the 1940s, infant and child milk distribution programs for supplementary feeding had become well established. Chile instituted a national health service (Servicio Nacional de Salud - SNS) that was similar to the British NHS in 1952 (17). It also had a historically active private sector, with the most prestigious hospitals being private and many doctors (including a number working in the public sector) having private practices. Public sector and white collar employees developed a separate insurance system that started offering primary care in the 1940s and in 1968 became a full-benefit plan using private physicians and allowing participants to opt out of the public health care system (SERMENA - National Medical Services for Employees) (17). An independent system of medical services was also established for each branch of the armed forces, including hospitals, clinics, and other facilities. For example, in 1958, Law 12.856 established a health council for the air force and a special fund for the medical expenses of armed forces retirees and dependents. Finally, an active but relatively limited voluntary sector has developed that includes services to fill the gaps of both the public and private systems. The majority of the voluntary sector is supported by religious charities while a few services are funded by non-sectarian groups, e.g., a national rehabilitation center for burned children (COANIQUEM).
Keywords
- aequorin
- contraction
- excitation
- heart failure
- sarcoplasmic reticulum