Nisha Chandra

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

A Randomized Trial of Intravenous Tissue Plasminogen Activator for Acute Myocardial Infarction with Subsequent Randomization to Elective Coronary Angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.

Determinants of blood flow to vital organs during cardiopulmonary resuscitation in dogs.

Whether blood flow during cardiopulmonary resuscitation (CPR) results from intrathoracic pressure fluctuations or direct cardiac compression remains controversial. From modeling considerations, blood flow due to intrathoracic pressure fluctuations should be insensitive to compression rate over a wide range, but dependent on the applied force and compression duration. If direct compression of the heart plays a major role, however, flow should be dependent on compression rate and force, but above a threshold, insensitive to compression duration. These differences in hemodynamics produced by changes in rate and duration form a basis for determining whether blood flow during CPR results from intrathoracic pressure fluctuations or from direct cardiac compression. Manual CPR was studied in eight anesthetized, 21 to 32 kg dogs after induction of ventricular fibrillation. There was no surgical manipulation of the chest. Myocardial and cerebral blood flows were determined with radioactive microspheres. At nearly constant peak sternal force (378 to 426 newtons), flow was significantly increased when the duration of compression was increased from 14 +/- 1% to 46 +/- 3% of the cycle at a rate of 60/min. Flow was unchanged, however, after an increase in rate from 60 to 150/min at constant compression duration. The hemodynamics of manual CPR were next compared with those produced by vest inflation with simultaneous ventilation (vest CPR) in eight other dogs. Vest CPR changed intrathoracic pressure without direct cardiac compression, since sternal displacement was less than 0.8 cm. At a rate of 150/min, with similar duration and right atrial peak pressure, manual and vest CPR produced similar flow and perfusion pressures. Finally, the hemodynamics of manual CPR were compared with the hemodynamics of direct cardiac compression after thoracotomy. Cardiac deformation was measured and held nearly constant during changes in rate and duration. As opposed to changes accompanying manual CPR, there was no change in perfusion pressures when duration was increased from 15% to 45% of the cycle at a constant rate of 60/min. There was, however, a significant increase in perfusion pressures when rate was increased from 60 to 150/min at a constant duration of 45%. Thus, vital organ perfusion pressures and flow during manual external chest compression are dependent on the duration of compression, but not on rates of 60 or 150/min. These data are similar to those observed for vest CPR, where intrathoracic pressure is manipulated without sternal displacement, but opposite of those observed for direct cardiac compression.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Experience With Primary Percutaneous Transluminal Coronary Angioplasty Compared With Alteplase (Recombinant Tissue-Type Plasminogen Activator) in Patients With Acute Myocardial Infarction : A Report From the Second National Registry of Myocardial Infarction (NRMI-2)

OBJECTIVESnWe sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI).nnnBACKGROUNDnPrimary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group.nnnMETHODSnData from NRMI-2 were reviewed.nnnRESULTSnFrom June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lytic-ineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic-eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA).nnnCONCLUSIONSnThese findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.

A Preliminary Study of Cardiopulmonary Resuscitation by Circumferential Compression of the Chest with Use of a Pneumatic Vest

BACKGROUNDnMore than 300,000 people die each year of cardiac arrest. Studies have shown that raising vascular pressures during cardiopulmonary resuscitation (CPR) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure.nnnMETHODSnTo produce periodic increases in intrathoracic pressure, we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR (vest CPR) with those of manual CPR. In phase 1 of the study, aortic and right-atrial pressures were measured during both vest CPR (60 inflations per minute) and manual CPR in 15 patients in whom a mean (+/- SD) of 42 +/- 16 minutes of initial manual CPR had been unsuccessful. Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made. In phase 2 of the study, short-term survival was assessed in 34 additional patients randomly assigned to undergo vest CPR (17 patients) or continued manual CPR (17 patients) after initial manual CPR (duration, 11 +/- 4 minutes) had been unsuccessful.nnnRESULTSnIn phase 1 of the study, vest CPR increased the peak aortic pressure from 78 +/- 26 mm Hg to 138 +/- 28 mm Hg (P < 0.001) and the coronary perfusion pressure from 15 +/- 8 mm Hg to 23 +/- 11 mm Hg (P < 0.003). Despite prolonged unsuccessful manual CPR, spontaneous circulation returned with vest CPR in 4 of the 29 patients. In phase 2 of the study, spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR (P = 0.14). More patients in the vest-CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation (6 of 17 vs. 1 of 17) and 24 hours after attempted resuscitation (3 of 17 vs. 1 of 17), but none survived to leave the hospital.nnnCONCLUSIONSnIn this preliminary study, vest CPR, despite its late application, successfully increased aortic pressure and coronary perfusion pressure, and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR. The effect of vest CPR on survival, however, is currently unknown and will require further study.

A Reappraisal of Mouth-to-Mouth Ventilation During Bystander-Initiated Cardiopulmonary Resuscitation A Statement for Healthcare Professionals From the Ventilation Working Group of the Basic Life Support and Pediatric Life Support Subcommittees, American Heart Association

Cardiopulmonary resuscitation (CPR) performed by bystanders clearly improves survival and victims of out-of-hospital cardiac arrest and other life-threatening conditions such as drowning and respiratory arrest.1 2 However, despite three decades of promulgation, CPR is not performed for the majority of victims who require lifesaving care.3 4 5 6 Studies have identified reticence to perform mouth-to-mouth ventilation as a significant barrier to more frequent performance of bystander CPR.1 7 8 9 10 11 12 13 In addition to acting as a barrier to initiation of CPR, the mouth-to-mouth ventilation component of CPR may have other adverse effects, such as promoting gastric insufflation14 15 16 17 or decreasing the percentage of time allocated to effective chest compression.18 19 20 nnBecause early CPR plays a central role in saving lives, the Ventilation Working Group of the Basic Life Support (BLS) and Pediatric Life Support Subcommittees of the AHA Emergency Cardiovascular Care (ECC) Committee reviewed the scientific evidence on mouth-to-mouth ventilation. The ECC Committee and its subcommittees prepare guidelines and recommendations for providing emergency cardiovascular care and cardiopulmonary resuscitation in the United States and will formally review and publish updated guidelines in the year 2000. Although this report represents a focused analysis and serves as a consensus statement regarding the role of mouth-to-mouth ventilation during CPR, it is not intended to change any current AHA recommendations or guidelines for performance of CPR. The specific purpose of this report is to review the historical rationale for providing mouth-to-mouth ventilation during CPR and to critically analyze, using the available scientific literature, the following questions: (1) Does assisted ventilation during CPR result in improved physiological status or survival? (2) Are there adverse effects that result from inclusion of mouth-to-mouth ventilation in basic CPR techniques? (3) Could mouth-to-mouth ventilation be deferred or delayed …

Augmentation of cerebral perfusion by simultaneous chest compression and lung inflation with abdominal binding after cardiac arrest in dogs.

Recent studies have demonstrated that for the same chest compression force during mechanical cardiopulmonary resuscitation (CPR), the carotid artery-to-jugular vein pressure gradient and carotid blood flow are increased when the phasic rise of intrathoracic pressure is enhanced by abdominal binding and simultaneous ventilation at high airway pressure with each chest compression (SCV). The objective of the present study was to assess whether cerebral blood flow is also enhanced, since it is known that fluctuations in intrathoracic pressure are transmitted to the intracranial space and affect intracranial pressure (ICP). In two series of pentobarbital-anesthetized dogs, one of two CPR techniques was initiated immediately after inducing ventricular fibrillation. Brain blood flow was measured by the radiolabeled microsphere technique immediately before cardiac arrest and at 1 and 3 minutes after commencing CPR. Evidence of adequate mixing of spheres and lack of sedimentation under these low-flow conditions was verified by correlation with brain venous outflow, comparison of the arterial concentration-time profile of spheres and a nonsedimentary marker (thallium-201 in solution), and use of multiple arterial sampling sites. During SCV CPR with abdominal binding, mean carotid artery pressure (60 +/- 3 mm Hg) was higher than that during conventional CPR (25 +/- 2 mm HG). Pulsations of ICP occurred that were in phase with chest compression and greater than jugular venous pressure. Mean ICP was higher during SCV (46 +/- 2 mm Hg) than conventional CPR (20 +/- 2 mm Hg). However, the net brain perfusion pressure gradient (carotid artery pressure - ICP) was greater with SCV (14 +/- 3 mm Hg) than with conventional CPR (5 +/- 0.4 mm Hg). Cerebral blood flow was significantly greater during SCV CPR (32 +/- 7% of prearrest cerebral flow) than during conventional CPR (3 +/- 2%). We conclude that SCV CPR combined with abdominal binding substantially improved brain perfusion by enhancing cerebral perfusion pressure in this experimental model.

Simultaneous chest compression and ventilation at high airway pressure during cardiopulmonary resuscitation.

In most patients blood flow during cardiopulmonary resuscitation (CPR) results from a rise in intrathoracic pressure rather than from direct heart compression. Intrathoracic pressure was increased by the use of positive-pressure ventilation synchronous with sternal compression in eleven arrested patients who were intubated. A computer system allowed 15-30 s periods of alternation between conventional CPR and new CPR (rate of 40/min, 60% compression duration, and simultaneous ventilation at airway pressures from 60 to 110 cm H2O). Compression force was identical with the two methods. New CPR increased mean systolic radial artery pressure significantly from 40.6 +/- 4.4 to 53.1 +/- 3.9 mm Hg for 14 runs in nine patients. In 15 runs in ten patients an index of carotid flow increased with new CPR to 252% (range 113-643%) of control values. Lowering airway pressure during a new CPR lowered flow index and arterial pressure, confirming that these increases with new CPR were due to higher intrathoracic pressure. Thus, increased airway pressure synchronous with sternal compression increases arterial pressure and likely blood flow during CPR in man. However, further studies of potential complications and long-term effects of new CPR, particularly on adequacy of ventilation, are needed before clinical implementation is undertaken.

Vest inflation without simultaneous ventilation during cardiac arrest in dogs: improved survival from prolonged cardiopulmonary resuscitation.

Myocardial and cerebral blood flow can be generated during cardiac arrest by techniques that manipulate intrathoracic pressure. Augmentation of intrathoracic pressure by high-pressure ventilation simultaneous with compression of the chest in dogs has been shown to produce higher flows to the heart and brain, but has limited usefulness because of the requirement for endotracheal intubation and complex devices. A system was developed that can produce high intrathoracic pressure without simultaneous ventilation by use of a pneumatically cycled vest placed around the thorax (vest cardiopulmonary resuscitation [CPR]). The system was first tested in a short-term study of the maximum achievable flows during arrest. Peak vest pressures up to 380 mm Hg were used on eight 21 to 30 kg dogs after induction of ventricular fibrillation and administration of epinephrine. Microsphere-determined myocardial blood flow was 108 +/- 17 ml/min/100 g (100 +/- 16% of prearrest flow) and cerebral flow was 51 +/- 12 ml/min/100 g (165 +/- 39% of prearrest). Severe lung or liver trauma was noted in three of eight dogs. If peak vest pressure was limited to 280 mm Hg, however, severe trauma was no longer observed. A study of the hemodynamics during and survival from prolonged resuscitation was then performed on three groups of seven dogs. Vest CPR was compared with manual CPR with either conventional (300 newtons) or high (430 newtons) sternal force. After induction of ventricular fibrillation, each technique was performed for 26 min. Defibrillation was then performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris: a randomized, double-blind, placebo-controlled trial.

The value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.