Co-expression of fibulin-5 and VEGF165 increases long-term patency of synthetic vascular grafts seeded with autologous endothelial cells.

Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.

The sheep as a model for coronary artery bypass surgery.

The sheep is considered to be a suitable model for cardiovascular surgery because of its ease of handling, size, and vascular anatomy which bears close resemblance to the human. Several difficulties, however, have limited the use of the sheep for such a purpose-mainly the high infection rate resulting from median sternotomy incision and its susceptibility to intractable ventricular fibrillation (VF) with the slightest manipulation of the heart, and even the risk of short periods of myocardial ischaemia. We have used the sheep model extensively to perform coronary artery bypass surgery and were successful in overcoming these difficulties. Fifty-seven adult female sheep were used to test a new anastomotic device for the creation of a sutureless connection between venous and arterial grafts and the coronary arteries. The study required full access to the heart and great vessels and mobilization of one of the internal mammary arteries. Changing to the left lateral thoracotomy (LLT) approach solved the initial fatal problems of postoperative infected median sternotomy incisions. Aggressive prophylactic treatment with anti-arrhythmic drugs, maintenance of normothermia and myocardial preconditioning rendered the heart much less vulnerable to manipulations and ischaemia. These measures have reduced the mortality rate from 45% to 0% (P <0.0001). With specific operative techniques and pharmaceutical interventions, the sheep can be effectively and safely used as a model for coronary artery surgery.

Three-dimensional electromechanical mapping: imaging in the operating room of the future.

BACKGROUND: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. METHODS: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. RESULTS: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. CONCLUSIONS: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction.

OBJECTIVES: This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping. BACKGROUND: The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue. METHODS: Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data. RESULTS: From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.

Hemodynamic evaluation of descending aortomyoplasty versus intra-aortic balloon pump performed in normal animals: an acute study.

OBJECTIVE: Aortomyoplasty is a surgical procedure that aims to induce hemodynamic benefits similar to those of the intra-aortic-balloon-pump (IABP). The objective of this study was to compare the coronary blood flow augmentation and afterload reduction produced by IABP and descending aortomyoplasty counterpulsation. METHODS: From a series of fifteen mongrel dogs (18-35 kg), eight underwent acute descending aortomyoplasty and seven had IABP application. Left anterior descending (LAD) coronary artery blood flow was measured using a Doppler flow probe. Left ventricular pressure in addition to aortic pressures both proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. All experiments were acute and performed in normal hearts. RESULTS: Descending aortomyoplasty induced a 27% increase in the LAD blood flow integral during assisted beats (14.0+/-6 ml/min integral compared to 10.8+/-4 ml/min integral in unassisted beats [P<0.001]). This was comparable to an 18% rise in the LAD blood flow integral during IABP counterpulsation (from 8.6+/-3 ml/min to 10.2+/-4 ml/min [P<0.001]). Conversely, while IABP counterpulsation reduced the left ventricular afterload by 16% (from 102+/-23 mmHg to 86+/-26 mmHg [P<0.001]), descending aortomyoplasty did not result in afterload reduction. CONCLUSIONS: Descending aortomyoplasty produces coronary blood flow augmentation comparable to that achieved by the IABP. This may be important for end-stage ischemic patients. However, afterload reduction achieved by the IABP was not reproduced during descending aortomyoplasty counterpulsation. The surgical technique of descending aortomyoplasty should be modified to attain afterload reduction, thus improving treatment for congestive heart failure patients.

Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs.

BACKGROUND: Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. METHODS AND RESULTS: Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non-laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment (P:<0.05) lowered mortality significantly, from 30% to 6.5%, after induction of MI. The infarct size in the LI dogs was reduced significantly (P:<0.0001) (52%) compared with NLI dogs. Histological observation of the infarct revealed a typical scar tissue in NLI dogs and cellularity in most of the LI dogs. Only 14+/-3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36+/-1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats. CONCLUSIONS: Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI.

A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small-bowel lesions.

BACKGROUND & AIMS: Wireless capsule endoscopy is a new, painless method of imaging the entire small bowel. It has not been compared with push enteroscopy. We compared the sensitivity, specificity, and safety of capsule and push enteroscopy in detecting small-bowel lesions. METHODS: Nine to 13 radiopaque, colored beads (3-6 mm diameter) were sewn in random order inside 9 canine small bowels, half within the first meter, and confirmed on x-ray. After recovery, the number, order, and color of beads were assessed in 23 capsule enteroscopies and 9 push enteroscopies in a random order. The surgeons, push enteroscopists, capsule video interpreters, and pathologist were blinded to the others' findings. RESULTS: The capsules identified more beads than push enteroscopy (median, 6 [range, 2-9] vs. 3 [range, 2-6 beads]; P < 0.001). The sensitivity of the capsule was 64% compared with 37% for push enteroscopy. The specificity was 92% for capsule enteroscopy and 97% for push enteroscopy. The capsules identified significantly more beads beyond the reach of the push enteroscope (median, 4 [range, 2-7] vs. 0; P < 0.0001). Hair, ingested plastic, ulceration, submucosal swelling, and worms were clearly identified by the capsule. The capsules passed safely through the animals with no significant histologic findings. CONCLUSIONS: Wireless capsule endoscopy detected more abnormalities in the small bowel than push enteroscopy.

Three-dimensional automatic quantitative analysis of intravascular ultrasound images.

Intravascular ultrasound (IVUS) has established itself as a useful tool for coronary assessment. The vast amount of data obtained by a single IVUS study renders manual analysis impractical for clinical use. A computerized method is needed to accelerate the process and eliminate user-dependency. In this study, a new algorithm is used to identify the lumen border and the media-adventitia border (the external elastic membrane). Setting an initial surface on the IVUS catheter perimeter and using active contour principles, the surface inflates until virtual force equilibrium defined by the surface geometry and image features is reached. The method extracts these features in three dimensions (3-D). Eight IVUS procedures were performed using an automatic pullback device. Using the ECG signal for synchronization, sets of images covering the entire studied region and corresponding to the same cardiac phase were sampled. Lumen and media-adventitia border contours were traced manually and compared to the automatic results obtained by the suggested method. Linear regression results for vessel area enclosed by the lumen and media-adventitia border indicate high correlation between manual vs. automatic tracings (y = 1.07 x -0.38; r = 0.98; SD = 0.112 mm(2); n = 88). These results indicate that the suggested algorithm may potentially provide a clinical tool for accurate lumen and plaque assessment.

Acute descending aortomyoplasty induces coronary blood flow augmentation.

BACKGROUND: Aortomyoplasty is a procedure aimed to improve cardiac output in patients suffering from heart failure. Stimulation of the latissimus dorsi muscle around the aorta produces hemodynamic effects similar to those of the intraaortic balloon pump. These may be maintained without the accompanying complications or the need for anticoagulation. The objective of this study was to test the acute effects of aortomyoplasty on coronary artery blood flow. METHODS: Eight mongrel dogs (18 to 30 kg) underwent acute descending aortomyoplasty. Several stimulation protocols were applied after wrapping of the latissimus dorsi muscle around the aorta in different surgical configurations. The left anterior descending coronary blood flow was measured using a transonic Doppler flow probe. Left ventricular and aortic pressures, proximal and distal to the aortomyoplasty site, were monitored continuously. RESULTS: Significant aortic diastolic pressure augmentation was expressed both as an increase in peak values, from 110 +/- 24 mm Hg to 120 +/- 24 mm Hg (p < 0.001) and as an increase in the diastolic integral, from 64 +/- 23 mm Hg x s to 84 +/- 37 mm Hg x s (p < 0.001). Concomitantly, peak left anterior descending coronary blood flow increased from 26 +/- 10 mL/min to 32 +/- 12 mL/min (p < 0.001). This was associated with an increase in the diastolic flow integral from 11 +/- 4 mL to 14 +/- 6 mL (p < 0.001). CONCLUSIONS: Descending aortomyoplasty induces significant augmentation of coronary blood flow. Optimal timing of muscle stimulation is important in achieving the best assist. This procedure may prove beneficial for end-stage ischemic patients.

Estimation of coronary blood flow by ECG gated cardiac thermography in open-chest conditions.

Thermography is suggested as a tool to estimate myocardial and coronary epicardial flow in open-chest heart surgery. To test the feasibility and compare various methods for coronary flow estimation in open-chest surgery, thermographic imaging was applied to eight open-chest dogs which were injected with cold saline into the aortic root. Blood flow in the left arterial descending (LAD) coronary vessel was measured by a transit-time flowmeter. ECG gated images were acquired for 20-30 s, while the cold saline (20 ml) was injected into the aortic root. Several flow levels were achieved during repeated hyperaemic response to transient occlusions of the LAD. A temperature response curve for each flow level was obtained by averaging over an edge-detected arterial segment for each image frame. Several indices were calculated from the temperature curve and correlated with the measured coronary flow. These include: an index based on a corrective heat transfer model (r = 0.69, p < 0.001), the slope of the descending part of the response curve (r = 0.76, p < 0.001), the peak temperature difference (r = 0.66, p < 0.001), and the area above the temperature response curve (r = 0.61, p < 0.01). As shown, coronary flow can be estimated quantitatively by intraoperative epicardial thermography, and may therefore provide important on-line information regarding blood flow during open-chest surgical procedures. Further studies are required for optimal application of this technique so as to increase its potential as a valid clinical tool.

Penile intracorporeal infusion--possible access to the systemic circulation. Pressure flow studies in dogs and humans.

OBJECTIVE: To assess penile intracorporeal infusion as a simple alternative method of intravenous access during the initial phase of fluid resuscitation in male patients. DESIGN: Laboratory pressure flow studies in dogs and in humans. SUBJECTS: 5 male mongrel dogs, and 10 male patients who were being investigated for psychogenic impotence (n = 5) or organic impotence (n = 5). INTERVENTIONS: Dogs- two 19G needles were inserted into the canine corpora cavernosa, one for fluid infusion, and the other for cavernosal pressure monitoring. Ringer's lactate solution was infused into the corpora cavernosa, through an infusion pump. The dogs were then bled until systolic blood pressure reached 60 mmHg, and resuscitated by transfusion of autologous blood into the corpora cavernosa. HUMANS: Ringer's lactate solution was infused into a corpus cavernosum through a 19G scalp vein needle. Pressure monitoring was done through another 19 G needle. MAIN OUTCOME MEASURE: Fluid flow rates and in humans time taken to insert an intracorporeal needle. RESULTS: Mean (SD) infusion rate through the canine corpora was 110 (22) ml/minute for Ringer's lactate solution and 109 (18) ml/minute for autologous blood. Mean infusion rate into the human corpora was 89.7 (12) ml/minute in the psychogenic impotent patients, and 88.2 (9) ml/minute in the organic impotent patients. Mean time taken to insert the needle was 15 (7) sec. CONCLUSIONS: An intracorporeal infusion line can be established in a short period of time and adequate quantities of fluids can be infused through the human and canine corpora cavernosa.

Modulation of the arterial coronary blood flow by asynchronous activation with ventricular pacing.

UNLABELLED: This study aims to test the assumptions that: (1) coronary arterial flow is attenuated in an early activated region by ventricular pacing; (2) asynchronous mechanical activation caused by ventricular pacing under controlled perfusion pressure and intact coronary tone is associated with reduced coronary flow compared to atrial pacing; and (3) abolishment of vascular tone under controlled perfusion pressure diminishes the expected difference in blood flow between atrial and ventricular pacing. Blood flow velocity (BFV) in the left anterior descending (LAD) and the left circumflex arteries (CFX) and a wall thickening index were measured in 14 open-chest dogs under normal conditions, and constant perfusion pressure. Four pacing sites were used: right atrium (RAp), mid-right ventricle (RVp), mid-left ventricle (LVp), and left ventricular apex (Apexp). Pacing modes were either sequential ventriculoatrial (VA) (protocol A, n = 7), or sequential atrioventricular (AV) (protocol B, n = 7), with a shorter AV difference (30 msec) than normal. RESULTS: BFV was decreased in the LAD during RVp and Apexp pacing by 9.7%-12.9% versus RAp and by 11.6%-14.6% versus LVp (P < 0.05). No BFV variations were observed in the CFX. Flow velocity conductance (FVC = mean blood flow velocity divided by the mean aortic pressure) was higher by 16%-28% in the CFX for the three ventricular pacing sites versus the atrial pacing, and higher by 14.1% +/- 6.1% only in LVp versus RAp pacing in the LAD (P < 0.05). Wall thickening index reduced during ventricular pacing in all three ventricular sites by 50%-64% (P < 0.05) compared to atrial pacing. Under constant perfusion pressure, LAD blood flow decreased with ventricular pacing as compared to right atrial pacing; this was particularly pronounced during the diastolic phase (16.6%-45.5%, P < 0.02). Normalized oscillatory flow amplitude (OFAn) was reduced in RVp pacing compared to RAp and LVp pacing (16.2 +/- 3.5 and 21.7% +/- 4.1%, respectively, P < 0.03). The variations in blood flow and OFAn disappeared with adenosine-mediated maximum vasodilatation. SUMMARY: (1) Mean and phasic flows are reduced in the early activated LAD region by ventricular pacing (RVp, Apexp). (2) Under controlled perfusion pressure and intact vascular tone, ventricular pacing compromises blood flow compared with atrial pacing. (3) This effect disappears when vascular tone is eliminated by intracoronary injection of adenosine, suggesting that the coronary autoregulation is responsible for some of the effects.

Self-expandable and highly flexible nitinol stent: immediate and long-term results in dogs.

We sought to investigate the acute and long-term patency rates and the histologic response of coronary arteries to a self-expandable nitinol coil stent. Twenty-two stents were implanted. Angiographic patency was demonstrated acutely in all but one dog, in which the stent was released in a small branch (1 mm); mismatch in stent-to-artery diameters resulted in vessel closure. Two dogs died from anesthesia overdose and two from bleeding within 24 hours. All dogs were treated with aspirin (80 mg/day) and warfarin (2.5 mg/day) for up to 1 month. Sixteen dogs were monitored for 1 to 2 weeks, 1 month, 3 months, 6 months, and 1 year and underwent subsequent angiography and histopathologic examination. Angiographic artery dimensions measured immediately after stent implantation (2.72 +/- 0.4 mm) did not differ from those noted at follow-up (2.68 +/- 0.44 mm, p not significant). Histologic examination showed outward stent pressure compressing the internal elastic membrane and media in most cases. Intimal hyperplasia started at 2 weeks and was most apparent at 3 and 6 months. Mean intimal thickness was 30.7 +/- 10.9 mu, 141.8 +/- 105.4 mu, 227.1 +/- 104.1 mu, 211.8 +/- 99.1 mu, and 170.1 +/- 42.7 mu at 1 to 2 weeks and 1, 3, 6 and 12 months, respectively. Therefore the nitinol self-expandable stent provokes a moderate cellular proliferative response that reaches its maximum in 3 to 6 months without further progression.

Quantitative sorting of normal and abnormal coronary flow wave form shapes.

The normal phasic flow wave form in an epicardial coronary artery has a distinct characteristic shape, which reflects the interaction between the coronary tree, myocardial function and hemodynamic conditions. Since clinical measurements of phasic coronary wave forms are becoming available, determination of abnormal coronary flow wave forms is important. We suggest here an objective and automatic method to discriminate between normal and abnormal flow wave forms based on the Karhunen-Loève Transform (KLT), and experimentally tested it. The normal flow domain was represented by the resting flow waves measured in the left anterior descending arteries in 31 anesthetized dogs. The abnormal flow conditions, imposed and tested experimentally, were varying stenosis severity and severely reduced left ventricular pressure. In addition, the effects of reactive hyperemia on the shape of the flow were examined. The sorting index was based on the mean-square error (MSE) calculated for each flow signal based on a truncated KLT expansion. The results show excellent discrimination between the normal and the abnormal groups. During reactive hyperemia, however, MSE did not change significantly. These results indicate that the shape of abnormal coronary flow wave forms can be identified and discriminated from normal wave forms.

Self-expandable Nitinol stent for cardiovascular applications: canine and human experience.

The initial experimental and clinical experience with the cardiovascular self-expandable Nitinol stent (vascular and coronary versions) is described. The stent is designed as a helical coil with two terminal balls that are used for restraining it on the delivery catheter. Upon release, the stent self-expands immediately. A temporary stent version continues with a long wire that can be removed by pulling it as a straight wire through a small profile catheter. The stent uncoils in its own groove upon removal, a relatively atraumatic procedure. The stents have been studied in dogs and in peripheral arteries in patients. The results show a transient nonocclusive proliferative response to the stent that is maximal at 3-6 mo. The removability of the permanent stent has been proven in dogs. The preliminary results in patients are encouraging and demonstrate its feasibility for permanent and potentially temporary arterial support.

In-vivo study of the mechanical properties of epicardial coronary arteries.

This study proposes a method to examine the in-vivo pressure-volume (P-V) relationship of an epicardial coronary artery. With the proximal left anterior descending (LAD) artery in a dog occluded, the distal LAD flow oscillates around zero. Integration of the flow with respect to time yields the intraluminal arterial segment volume changes in the region between the site of occlusion and the flow probe. The distal LAD pressure is measured via a diagonal branch. The segmental P-V relationship exhibits a hysteresis loop. The area bound by the hysteresis loop corresponds to the energy loss on the arterial wall during one cycle (12.63 +/- 8.25 [erg.cm-1], n = 7), while the dynamic arterial compliance is calculated based on the ratio of the volume to pressure excursions (1.13 +/- 0.73 [ml.mmHg-1.cm-1.10(-4)]). These results represent first estimates of the in-vivo mechanical properties of the coronary arterial wall based on P-V measurements.

Pressures generated by rib cage and abdominal compressions during cardiopulmonary resuscitation.

When the rib cage and abdomen are compressed during cardiopulmonary resuscitation (CPR), the effect on intrathoracic pressure, and therefore on haemodynamics, cannot be quantitatively predicted without a physiologically based mathematical model of chest wall dynamics. Using such a model, we compared model simulations of pleural Ppl and abdominal Pab pressures with those from dog experiments in which the compression of the rib cage was delayed from 0 to 500 ms after compression of the abdomen. Integrals of Ppl and transdiaphragmatic pressure, Pdi = Pab-ppl, over their positive and negative values during a cycle were chosen as indices of driving pressures for cardiac output. Both from the model output and experimental data, we found that the positive ppl integral PPI tends to increase with a longer delay between rib cage and abdominal compressions. The negative ppl integral NPI, however, tends to decrease according to the model predictions and data. Furthermore, the positive and negative integrals of Pdi also tend to change with delay time in the opposite way, as shown by both the model simulations and the experiments. Our results show that chest wall tissues modify the externally applied pressures, thereby not allowing us to use the externally applied pressure sources directly as the driving pressure of the cardiovascular system under study. The optimal conditions for haemodynamics during CPR require a compromise between the positive and negative integral indices. Prediction of the optimal haemodynamics from externally applied pressures requires the coupling of appropriate physiological models of chest wall dynamics and haemodynamics.

Effect of vest cardiopulmonary resuscitation rate on cardiac output and coronary blood flow.

We studied the effect of CPR rate on the hemodynamic indices of surgically instrumented canine experimental models. Using pneumatic vest CPR, we applied simultaneous rib cage and abdominal compressions at rates of 1 to 12 Hz. CPR with 2-Hz frequency yielded the highest aortic and coronary flows (252 +/- 14 and 6.8 +/- 1.1 ml/min vs. 178 + 12 and 0.96 +/- 0.08 ml/min at 1 Hz, respectively; p less than .005). The validity of the present American Heart Association recommendation for 1-Hz CPR rate would benefit from further studies.