The diagnostic impact of prehospital 12-lead electrocardiography.

STUDY HYPOTHESIS: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital diagnostic accuracy is improved compared with single-lead telemetry. POPULATION: One-hundred sixty-six stable adult patients who sought paramedic evaluation for a chief complaint of nontraumatic chest pain. METHODS: One-hundred fifty-one prehospital 12-lead ECGs of diagnostic quality were obtained by paramedics on 166 adult patients presenting with nontraumatic chest pain. Paramedics and base station physicians were blinded to the information on acquired prehospital 12-lead ECGs and treated patients according to current standard of care-clinical diagnosis and single-lead telemetry. Final hospital diagnoses were classified into three groups: acute myocardial infarction (24); suspected angina or ischemia (61); and nonischemic chest pain (66). Paramedics and base station physicians' clinical diagnoses and prehospital and emergency department ECGs were similarly classified and compared. Prehospital and ED 12-lead ECGs were read retrospectively by two cardiologists. RESULTS: Paramedics achieved a high success rate (98.7%) in obtaining diagnostic quality prehospital 12-lead ECGs in 94.6% of eligible prehospital patients. For patients with acute myocardial infarction, prehospital ECG alone had significantly higher specificity than did the paramedic clinical diagnosis (99.2% vs 70.9%; P less than .001), and significantly higher positive predictive value (92.9% vs 32.7%; P less than .001). For patients with angina, combining the paramedic clinical diagnosis and the prehospital ECG significantly improved sensitivity (90.2% vs 62.3%; P less than .001) and increased negative predictive value (88.9% vs 71.3%; P less than .02) compared with paramedic clinical diagnosis alone. There was a high concordance between prehospital and ED ECG diagnosis (99.3% for acute myocardial infarction and 92.8% for angina). Furthermore, ten patients whose prehospital ECGs demonstrated ischemia and who had final hospital diagnoses of angina or acute myocardial infarction were mistriaged by paramedics and/or received no base station physician-directed therapy. CONCLUSION: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital 12-lead ECGs have the potential to significantly increase the diagnostic accuracy in chest pain patients, approach congruity with ED 12-lead ECG diagnoses, and may allow for consideration of altering and improving prehospital and hospital-based management in this patient population.

Steroid-induced enhancement of functional recovery of postischemic, reperfused myocardium in conscious dogs.

The effects of methylprednisolone sodium succinate (20 mg/kg, intravenously administered) on the time course of functional recovery of myocardium following a 15-minute coronary artery occlusion period and subsequent 5 hour reperfusion period were studied in chronically instrumented, conscious dogs. In comparison to a control group, animals receiving methylprednisolone 90 minutes prior to coronary occlusion demonstrated less depression of regional segment shortening following 15 minutes of reperfusion (52 +/- 13% vs control levels of 23 +/- 7% of preocclusion values) and improved recovery at 5 hours postreperfusion (106 +/- 6% vs control levels of 54 +/- 4% of preocclusion values). In animals receiving methylprednisolone immediately prior to reperfusion, there was also similar recovery of segment shortening at 5 hours (97 +/- 3%). In contrast, dogs receiving methylprednisolone 15 minutes after the onset of reperfusion or sodium succinate (5.5 mg/kg, intravenously administered) 90 minutes prior to occlusion demonstrated no improvement in recovery of function. Experiments in dogs not subjected to coronary occlusion documented that methylprednisolone sodium succinate lacked inotropic and vasodilator properties. The results suggest that methylprednisolone administered prior to or during coronary artery occlusion but not after reperfusion enhances the functional recovery of hypokinetic, postischemic, reperfused myocardium. These effects are unrelated to any direct hemodynamic action of steroids or to the sodium succinate salt.

Spontaneous recovery of left ventricular function following acute anterior myocardial infarction.

Four patients with acute anterior wall myocardial infarction showing spontaneous and marked improvement in systolic left ventricular function are described. All 4 patients showed abnormal Q waves and severe wall motion abnormalities soon after acute infarction. In all 4 patients, at least some regeneration of R-wave forces occurred and the regional wall motion in the involved area of the left ventricle improved dramatically without coronary angioplasty or surgical revascularization during the intervening period. The improvement in left ventricular function was attributed to spontaneous increase in nutrient flow to the involved area. It is concluded that Q waves and severe wall motion abnormalities do not necessarily indicate irreversible scar formation.

Comparative effects of inotropic agents on coronary and systemic hemodynamics of conscious dogs: actions of milrinone, dopamine, ouabain and MCI-154.

The hemodynamic actions of a new inotropic agent, MCI-154, were compared to dopamine, ouabain and milrinone in conscious, chronically instrumented dogs. MCI-154 and milrinone produced similar hemodynamic changes: increases in heart rate, diastolic coronary blood flow velocity and peak positive dP/dt. Neither agent had significant effects on arterial pressure while both drugs reduced left ventricular end-diastolic pressure in a dose-related fashion and myocardial segment length, indicating a decrease in diastolic left-ventricular size. MCI-154 was found to be approximately twice as potent as milrinone. In contrast, dopamine and ouabain produced little change in left ventricular end-diastolic pressure or myocardial segment length during diastole, while both drugs produced increases in arterial and left ventricular systolic pressures. An increase in left ventricular afterload was not observed with either MCI-154 or milrinone, highlighting an important advantage of the latter compounds.

Improvement of postischemic, contractile function by the calcium channel blocking agent nitrendipine in conscious dogs.

The effect of the new calcium channel blocking agent, nitrendipine, on recovery of contractile function following a 10-min left anterior descending coronary artery occlusion was studied in conscious dogs instrumented with sonomicrometers in the subendocardium of ischemic and normal regions. Nitrendipine (1.0 and 2.5 micrograms/kg/min i.v.) or drug vehicle was administered 30 min prior to the onset of coronary artery occlusion and continued for 30 min following reperfusion accomplished by inflation and deflation of a vascular balloon cuff. Nitrendipine produced a dose-related reduction in arterial pressure and an increase in heart rate and left circumflex coronary blood flow velocity. At 6 h following reperfusion in control dogs (N = 8), segment shortening was significantly reduced from control levels (71 +/- 10% of control). In comparison, dogs pretreated with nitrendipine (3 micrograms/kg/min i.v.) (n = 8) had significantly greater recovery of segment shortening throughout the reperfusion period (102 +/- 10% of control at 6 h following reperfusion). The data demonstrate that pretreatment with the calcium channel blocking agent enhances the recovery of function in postischemic, reperfused, "stunned" myocardium.

Time course of recovery of "stunned" myocardium following variable periods of ischemia in conscious and anesthetized dogs.

Persistence of regional contractile dysfunction after restoration of blood flow to transiently ischemic myocardium has been well described. To date, most studies have been performed in anesthetized animals. The present investigation compared the time course of recovery of regional segment shortening (percentage of segment shortening) in anesthetized versus conscious dogs subjected to a brief period of total occlusion of the left anterior descending coronary artery. Periods of occlusion lasting 5, 10, and 15 minutes were followed by 3 hours of reperfusion. Dogs anesthetized with sodium pentobarbital (30 mg/kg intravenously) had a significantly higher heart rate and blood pressure and lower dP/dt than conscious dogs. Coronary artery occlusion resulted in similar degrees of regional dyskinesis or akinesis, indicative of severe myocardial ischemia, in all experiments. During reperfusion, a gradual return of contractile function toward baseline was observed. At the end of the first 15 minutes of reflow, dogs subjected to 5 minutes of coronary occlusion demonstrated approximately 70% of control segment shortening in the previously ischemic zone. Animals subjected to 10- and 15-minute periods of coronary artery occlusion showed approximately 60% and 40% of control segment shortening at the same time point, respectively. The remainder of the 3-hour reperfusion period was characterized by a more gradual recovery of regional segment function. No differences were observed between anesthetized and conscious animals. It is concluded that the time course of functional recovery of postischemic reperfused myocardium is directly related to the duration of coronary occlusion and is similar in conscious and anesthetized dogs.

Cardiovascular actions of a new dihydropyridine calcium antagonist, 8363-S: comparison with nifedipine and nicardipine in awake, unsedated dogs.

The systemic and coronary hemodynamic actions of a new dihydropyridine, 8363-S, were compared with nifedipine and nicardipine in conscious, instrumented dogs following intravenous and oral administration. All agents produced similar reductions in arterial and ventricular pressures and increases in heart rate, dP/dt, and coronary blood flow velocity, following intravenous infusion. Following oral administration, all agents had qualitatively similar actions; however, there was a marked difference in potency. 8363-S was found to be most potent in that 0.25 mg/kg produced equivalent or larger changes from control than 0.5 mg/kg nifedipine or 1.0 mg/kg nicardipine. Furthermore, 8363-S had a longer duration of action following oral administration. The results suggest that important differences in bioavailability exist amongst dihydropyridines which may have important therapeutic implications.

Determination of in utero fetal rat heart rate by ultrasound.

A technique for in utero determination of rat fetal heart rat in conscious and anesthetized animals is described. Fetal heart rate was analyzed using echocardiography by recording two-dimensional ultrasound images along with the derived M-mode tracing. This method allows for the simultaneous and sequential analysis of both maternal and fetal heart rate after exposure to therapeutic or environmental agents. When compared to other techniques, this noninvasive approach can clearly yield a more accurate assessment of drug effects on the fetal cardiovascular system. The method eliminates the influence of surgical manipulation on cardiac activity. More importantly, this approach can avoid the use of cardiodepressant anesthetic drugs and their potential interaction with agents under investigation. This method is thereby more sensitive and specific for determining the effects of compounds under study than previously described techniques. To illustrate this system, fetal heart rates are compared after maternal propranolol administration in conscious and anesthetized animals.

Stimulation of myocardium during reperfusion injury by a new inotrope-vasodilator agent, MCI-154.

The systemic and coronary hemodynamic actions of a newly synthesized inotropic agent structurally related to milrinone and amrinone, MCI-154 (0.5-4.0 micrograms/kg/min IV), were studied in 2 groups of conscious, chronically instrumented dogs with normal or depressed postischemic, reperfused myocardium after a 15-min coronary artery occlusion. In an additional group of control experiments, the time course of recovery of postischemic, reperfused myocardium was studied to verify the constancy of regional segment shortening in the previously ischemic zone during the time corresponding to drug infusion. Similar inotropic actions of MCI-154 were observed in both normal and postischemic, reperfused hearts, indicating significant contractile reserve to be present in 'stunned' myocardium. Global contractility as measured by peak positive dP/dt was significantly increased in both groups. In postischemic, reperfused myocardium 90 min after initiation of reflow, regional segment function remained depressed at 44% of control but improved to 93% of control after administration of MCI-154. In addition, MCI-154 produced significant dose-related decreases in mean arterial pressure, left ventricular end-diastolic pressure, end-diastolic segment length, and diastolic coronary vascular resistance. The data demonstrate that in addition to producing beneficial hemodynamic changes, MCI-154, a new non-sympathomimetic inotropic agent, markedly enhances regional contractility of postischemic, reperfused myocardium.

Recovery of contractile function in post-ischaemic reperfused myocardium of conscious dogs: influence of nicorandil, a new antianginal agent.

The effects of intravenous administration of nicorandil, a new antianginal agent, on the recovery of regional myocardial contractile function after a 10 minute coronary artery occlusion were studied in chronically instrumented conscious dogs. Compared with the control group nicorandil administration resulted in an increase in heart rate and a decrease in blood pressure with an overall increase in the double product during the preocclusion period, no significant difference in double product during ischaemia, and a significant decrease in double product during reperfusion. After reperfusion the return of regional contractile function was appreciably enhanced in the nicorandil treated group. These effects were seen immediately after coronary reflow and persisted throughout the reperfusion period. These data suggest that nicorandil protects ischaemic cardiac tissue, and that the beneficial actions may be mediated through a reduction in left ventricular afterload.

Slow channel calcium activators, a new group of pharmacological agents.

Specific calcium channels in myocardium and vascular smooth muscle and pharmacologic agents which possess the ability to block them have been the subject of intense research over the past several years. Many studies have utilized dihydropyridine derivatives (e.g. nifedipine, nitrendipine, nisoldipine) which have been shown to be efficacious inhibitors of calcium influx through voltage sensitive slow channels. Administration of these agents results in vascular smooth muscle relaxation and negative inotropic effects. Recently, novel dihydropyridines such as Bay k 8644, CGP 28 392 and YC-170, with actions diametrically opposed to those of compounds typified by nifedipine have been synthesized. These agents demonstrate vaso-constrictor and positive inotropic effects - actions which might be expected of compounds capable of stimulating the transmembrane influx of calcium into vascular smooth muscle and myocardium. Actions of Bay k 8644 and CGP 28 392 studied in vitro and in vivo have also shown that pharmacological blockade of beta or alpha adrenergic receptors does not influence the direct effects of these agents. Future analogs, with similar but more selective actions on myocardial calcium channels, may prove useful in the management of pathologic states characterized by insufficient contractile function of the heart.

Hemodynamic actions of nicorandil, a new antianginal agent, in the conscious dog.

We studied the hemodynamic effects of nicorandil (SG-75) and nitroglycerin in conscious dogs before and after beta-adrenergic receptor blockade. Nicorandil (25-300 micrograms/kg/min) and nitroglycerin (5-60 micrograms/kg/min) produced increases in heart rate and decreases in aortic and left ventricular pressures. In the doses studied, nicorandil caused greater decreases in aortic and left ventricular systolic pressure than nitroglycerin; however, nitroglycerin reduced left ventricular end-diastolic pressure to a greater degree. Nicorandil but not nitroglycerin produced an increase in cardiac output secondary to an increase in heart rate. Global contractility (peak positive dP/dt) was increased in a dose-related manner during nicorandil infusion before beta-blockade. In spite of marked hypotensive responses to higher doses, mean coronary blood flow and coronary conductance were increased by nicorandil. In contrast, both parameters were reduced during nitroglycerin infusion. The effects of nicorandil on coronary blood flow were unaltered by beta-adrenergic blockade, suggesting that metabolic autoregulation is not an important mediator of the response. Nicorandil (75-300 micrograms/kg/min) produced a dose-related increase in transmural myocardial blood flow with the greatest increases in perfusion occurring in the subepicardium and midmyocardium. The results of the present study demonstrate that despite structural similarities, nicorandil and nitroglycerin have varying hemodynamic spectra.

Positive inotropic actions of the calcium channel stimulator, Bay k 8644, in awake, unsedated dogs.

The hemodynamic effects of the dihydropyridine derivative Bay k 8644, a new calcium agonist with positive inotropic actions, were studied in instrumented conscious dogs before and after beta adrenergic blockade with propranolol. Intravenous Bay k 8644 (2, 4, 8 and 20 micrograms/kg/min) produced dose-related increases in arterial and left ventricular systolic pressures and myocardial contractility (+dP/dt; % segment shortening). Coronary blood flow velocity was increased at higher doses. Prior administration of propranolol produced no significant alteration of the hemodynamic effects of Bay k 8644. Increases in arterial and left ventricular pressures produced by Bay k 8644 were controlled by intravenous infusion of sodium nitroprusside with resulting enhancement of positive inotropic effects. The results demonstrate that the hemodynamic responses to this novel calcium agonist with positive inotropic properties are not mediated via beta adrenergic mechanisms and control of increases in arterial pressure lead to enhanced regional contractility.

Cardiovascular effects of the nifedipine analog, CGP 28 392, in the conscious dog.

The cardiovascular profile of the nifedipine analog, CGP 28 392, was studied in instrumented conscious dogs. CGP 28 392 (25, 50, 100, and 150 micrograms/kg) was administered intravenously, and systemic and coronary hemodynamics monitored with and without prior treatment with nifedipine, phentolamine, propranolol, or atropine. CGP 28 392 increased arterial blood pressure and coronary vascular resistance in a dose-related manner and reduced heart rate. No positive inotropic actions were observed. All hemodynamic effects of CGP 28 392 were blocked by nifedipine but were unaltered by phentolamine. The decrease in heart rate was attenuated by atropine and propranolol. These data demonstrate that the actions of CGP 28 392 are diametrically opposed to those of the dihydropyridine slow channel calcium entry blockers and are specifically blocked by nifedipine. The cardiovascular actions of this compound (with the exception of bradycardia) are not mediated through the autonomic nervous system, and interactions with other pharmacological agents suggest that CGP 28 392 has calcium channel activating properties.

A microcomputer-based package for determination of regional and global cardiac function and coronary hemodynamics.

A multichannel data acquisition package for reduction of systemic and coronary hemodynamic data that utilizes a personal microcomputer is described. The system provides a printout of heart rate, maximal rate of left ventricular pressure development (+dP/dt), maximal rate of ventricular relaxation (-dP/dt), absolute and normalized myocardial segment lengths, the degree of shortening of the segment over the cardiac cycle, systolic, diastolic, and mean coronary blood flow velocities, left ventricular systolic and end diastolic pressures, and systolic, diastolic, and mean aortic blood pressure from six channels of input data. Obtained values are precisely linked to the cardiac cycle. To illustrate the output of this system, data obtained by reading strip-chart records are compared to microcomputer-derived values in conscious, instrumented dogs.