In the Syrian cardiomyopathic hamster heart, abnormal cellular calcium regulation, resulting in cellular calcium overload, is believed to play a role in the pathogenesis of cardiac hypertrophy and failure. Alternatively, the primary abnormality may be coronary vasospasm, resulting in reperfusion-induced necrosis. According to the latter hypothesis, only those cells that suffer an ischemic insult would contain elevated calcium levels. To determine whether a generalized elevation in myocytic calcium exists in myopathic hamster hearts, we measured cellular and subcellular calcium concentrations by electron probe microanalysis in cryosections of 50-day and 96-day myopathic and control hearts, rapidly frozen in vivo. Total calcium content of ventricular homogenates from each group was also measured by atomic absorption spectrophotometry. No significant differences hi subcellular calcium were found by electron probe microanalysis among 50-day and 96-day myopathics and their age-matched controls. In 50-day myopathic and control hearts, mitochondria! calcium was 0.7±0.2 and 0.9±0.2, respectively, and A-band calcium was 3.0±0.4 and 2.6±0.4 nunol calcium/kg dry wt(±SEM). Results from 96-day animals were similar. Localized regions of elevated calcium were found only at sites of necrotic foci: in Na + -loaded cells (mitochondria: 4.7±1.3 (SEM) mmol/kg dry wt), in dying cells (mitochondria: 72±22 (SEM) mmol/kg dry wt) or as extracellular deposits (7-10 mol/kg dry wt). Total calcium content of hearts from myopathic hamsters, as determined by atomic absorption spectrophotometry, was also 13 times (50-day) and 50 times (96-day) higher than controls. These results demonstrate that there is a marked heterogeneity in cellular calcium content in myopathic hamster hearts, but the data do not support the hypothesis of a generalized cellular calcium overload. 9 In view of the early onset of many of these changes in Ca 2+ metabolism, it has been proposed that a general elevation of intracellular Ca 2+ may be an important initiating or aggravating factor in the etiology of the disease.10 " Alternatively, it has been proposed by Sonnenblick and coworkers 12 that the primary defect responsible for development of heart failure in myo hamsters may not be an abnormality in Ca 2+ handling by the myocytes themselves but an increased reactivity of the coronary arteries and arterioles. They and others have provided evidence for the existence, in myo hamsters, of coronary vasospasm in situ 13 31920 Ca 2+ content of isolated mitochondrial fractions has also been shown to be significantly elevated in myo hearts.1120 The approaches used in these studies are, however, limited in their ability to identify whether the observed elevation in cardiac and/or mitochondrial Ca 2+ is a homogeneous phenomenon throughout the heart. An alternative methodology, which avoids the problems associated with measurements of total tissue Ca 2+ by AA, is electron probe microanalysis (EPMA) of intracellular and subcellular concentrations of Ca 2+ and other elements in ...

The strategy of prehospital activation by the emergency medical system (EMS) in patients with ST-elevation myocardial infarction (STEMI) has been poorly adopted among the US hospitals that currently offer 24/7 primary percutaneous coronary intervention. In this study, we report a single center experience after the implementation of this strategy. From 2008 to 2011, we identified a total 188 STEMI patients (age 65 ± 15 years) presenting via EMS for primary percutaneous coronary intervention. Of these, 112 (59.6%) underwent prehospital activation (EMS group), whereas the remaining 76 (40.4%) underwent emergency department activation [emergency department (ED) group]. Baseline demographic characteristics were similar between both groups. The overall median door-to-balloon (DTB) time was 49 ± 14 minutes. Patients undergoing prehospital activation had on average significantly lower overall DTB times (EMS 44 ± 11 minutes vs. ED 57 ± 15 minutes; P < 0.001). Concordantly, DTB times <60 minutes were much more commonly achieved with this strategy (EMS 95.5% vs. ED 64.5%; P < 0.001). Fallouts beyond the recommended 90-minute DTB time were seen among ED patients only. No difference in in-hospital death (EMS 5.4% vs. ED 6.6%; P = 0.75) or cumulative 30-day mortality (EMS 6.3% vs. ED 7.9%; P = 0.68) was observed between both groups. However, on average, EMS patients had higher postinfarct left ventricular ejection fraction (EMS 48 ± 9.5% vs. ED 39 ± 14.6%; P = 0.004). Differences in DTB time and left ventricular ejection fraction remained significant after adjusting for differences in baseline characteristics. In conclusion, the prehospital activation strategy is largely effective and should be systematically adopted in the treatment scheme of STEMI patients to lower mechanical reperfusion times and reduce the potential for untoward clinical outcomes.