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Biomedical subjects

D Alyono

Publications and source records attributed to D Alyono.

At least 19 recordsLinked to original sources

Saphenous vein graft reconstruction of an unclippable giant basilar artery aneurysm performed with the patient under deep hypothermic circulatory arrest: technical case report.

OBJECTIVE AND IMPORTANCE: Effective treatment for unclippable giant vertebrobasilar aneurysms remains unclear. We present the first reported case of a giant vertebrobasilar aneurysm being successfully treated with trapping of the aneurysm and internal carotid artery to basilar artery bypass with a saphenous vein graft that was performed with the patient under hypothermic circulatory arrest. CLINICAL PRESENTATION: A 15-year-old female patient with a history of probable subarachnoid hemorrhage and chronic headaches presented with a relatively acute exacerbation of her headache, nausea, vomiting, and weakness. Imaging studies revealed a 4 x 4 x 3-cm vertebrobasilar aneurysm, supplied by an angiographically dominant right vertebral artery and causing significant brain stem compression. INTERVENTION: Initially, a petrosal approach with a hearing-preserving partial labyrinthectomy was used to perform a right external carotid artery to posterior cerebral artery bypass with saphenous vein. Delayed occlusion of the right vertebral artery with an intraluminal balloon was planned; however, intraoperative angiography revealed poor graft flow, presumably because of the small size of the posterior cerebral artery. Postoperative graft occlusion was anticipated. During this same time interval, the patient deteriorated neurologically. Brain imaging failed to reveal evidence of cerebral infarction. The patient underwent subsequent surgery. After a total petrosectomy, the aneurysm was trapped, an aneurysmectomy was performed, and, with the patient under deep hypothermic circulatory arrest, a new interposition saphenous vein graft was inserted between the internal carotid and basilar arteries. Excellent flow was observed angiographically. At her 4-month follow-up examination, the patient had improved to near baseline. CONCLUSION: We present a technically challenging but safe and definitive treatment option for an unclippable giant vertebrobasilar aneurysm. Using cranial base approaches and hypothermic circulatory arrest techniques, aneurysmal trapping and successful bypass grafting directly into the basilar artery was performed.

Adolescent↗

Management of AIDS-related pneumothorax.

BACKGROUND: Pneumothorax (PTX) occurs in 5% of patients with acquired immunodeficiency syndrome (AIDS) infected with Pneumocystis carinii pneumonia, and up to 50% of those will die during hospitalization. The treatment strategies for managing AIDS-related PTXs are often complex and ineffective at treating the PTX, and they can prolong hospitalization. METHODS: We reviewed our experience with 36 male patients with AIDS treated for 44 PTXs over a 2.5-year period to determine if a particular therapeutic approach could allow for an earlier recovery and effective treatment of the PTX. All patients had current or prior history of Pneumocystis carinii pneumonia infection, and the CD4+ T-lymphocyte counts were less than 100/microL in 100%. RESULTS: Twenty-seven patients with 31 PTXs were discharged from the hospital. Of these 31 PTXs, 21 had resolved at the time of the patient's discharge from the hospital, and the other 10 PTXs were converted from Pleurevac (Deknatel, Inc, Fall River, MA) drainage to a Heimlich valve for persistent bronchopleural fistula after more than 15 days of conventional treatment. The PTXs were effectively managed by tube thoracostomy alone in 18/44 PTXs (41%), tube thoracostomy plus sclerosing therapy in 2/8 PTXs (25%), and thoracotomy with blebectomy and pleurodesis in 1/3 PTXs (33%). Nine of 11 of the procedure-related PTXs responded to tube thoracostomy alone; the other 2 PTXs were converted from Pleurevac drainage to a Heimlich valve and allowed for patient discharge from the hospital in less than 10 days. Nine patients with 13 PTXs died during hospitalization. Four of these 9 patients (44%) had bilateral PTXs, and 8/9 (89%) were being treated by tube thoracostomy with Pleurevac suction for persistent bronchopleural fistula in the intensive care unit at the time of death. The 8 patients treated for 10 PTXs with a Heimlich valve had effective management of the PTX, had no morbidity associated with the Heimlich valve and no in-hospital mortality, and were discharged from the hospital to home or a hospice setting. CONCLUSIONS: The management of AIDS-related PTXs is complex and often associated with a destructive pulmonary process and other systemic disease conditions related to AIDS that result in ineffective resolution of the PTX, a prolonged hospitalization, and a high mortality. In our experience, there is a lesser role for managing the PTXs with sclerosing therapy or thoracotomy. Patients with advanced AIDS complicated by PTXs with bronchopleural fistula can be converted from a Pleurevac drainage system to a Heimlich valve with no apparent morbidity or mortality, and managed as an outpatient, thereby potentially shortening hospitalization and facilitating an earlier discharge from an acute care setting.

AIDS-Related Opportunistic Infections↗

Platelet membrane glycoproteins and microvesicles in blood from postoperative salvage: a study in cardiac bypass patients.

BACKGROUND: Transfusion of blood collected by intraoperative and postoperative salvage systems has been linked to the development of thrombocytopenia and disseminated intravascular coagulation. Although functional defects have been reported in platelets from unwashed salvaged blood, platelet membrane glycoprotein (GP) composition, a potentially important determinant of function and survival, has not been studied. STUDY DESIGN AND METHODS: Platelets from 22 patients whose blood was salvaged at the completion of surgery were analyzed and compared to platelets obtained from the venous blood from the same patient. Platelet membranes were stained with fluorescein isothiocyanate-conjugated CD41a monoclonal antibody (anti-GPIIb/IIIa) to identify platelets, a phycoerythrin-conjugated monoclonal antibody, CD62 (anti-P-selectin) to identify activated platelets, and CD42b (anti-GPIb) or anti-GPIb/IX to assess GPIb. Samples were analyzed with a flow cytometer using software. RESULTS: Platelets obtained from salvaged blood demonstrated lower GPIb expression (CD42b and GPIb/IX monoclonal antibody binding), higher P-selectin expression, and greater numbers of platelet-derived microvesicles. CONCLUSION: The clinical significance of transfusing blood containing activated platelets and microvesicles merits investigation.

Blood Platelets↗

1-Deamino-8-D-arginine vasopressin (DDAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass.

1-deamino-8-D-Arginine vasopressin (DDAVP) shortens the bleeding time in some patients with platelet dysfunction and decreases blood loss in some cardiopulmonary bypass patients. We studied platelet membrane glycoproteins in patients with von Willebrand disease (vWD), disorders of platelet function, and in cardiopulmonary bypass patients after infusion of 0.3 microgram/kg of DDAVP. Platelets from 8 cardiopulmonary bypass patients, receiving DDAVP immediately after surgery, were compared to those of 14 patients not receiving DDAVP. We also studied 12 patients with vWD, and 8 patients with platelet dysfunction receiving DDAVP. Fixed platelets, stained with monoclonal fluorescein (FITC)-labeled antibodies directed against GPIb (CD42b antigen), GPIb/IX, GPIIb/IIIa (CD41a antigen), CD63 antigen (a platelet activation protein), and P-selectin (CD62 antigen) were studied by flow cytometry. Binding of CD42b monoclonal antibody (MoAb) and anti-GPIb/IX to platelets from both groups of bypass patients increased during the 18-20 hr after surgery, but the group receiving DDAVP showed the greater increase (P = 0.032). Platelets from patients receiving DDAVP for vWD or for platelet dysfunction, had increases in CD42b MoAb and anti-GPIb/IX binding (P < 0.01) that coincided with shortening of their bleeding time. No changes were seen in binding of other antibodies. When platelets from normal donors were incubated with DDAVP for 20 hr, there were increases in platelet surface CD42b MoAb binding, while immunogold-stained transmission electron micrographs of permeabilized platelets demonstrated decreases in cytoplasmic CD42b MoAb binding. DDAVP increases platelet membrane GPIb expression in a variety of patients and may account for improvement in hemostasis seen in some studies. Redistribution of GPIb from the cytoplasm to the membrane may account for this increased expression.

Adult↗

Magnesium deficiency prolongs myocardial stunning in an open-chest swine model.

The effect of magnesium deficiency on postischemic myocardial dysfunction (myocardial stunning) in an open-chest swine model was studied. Twelve swine were assigned either to low magnesium diet or control diet. Myocardial stunning was assessed by measuring regional wall thickening by epicardial Doppler before and after brief occlusion (8 min) of the left anterior descending coronary artery. Serum magnesium levels decreased significantly in the experimental group only. Glutathione levels were 42.6% lower in the magnesium deficient swine than in controls. Stunning time was significantly prolonged from 32.8 +/- 3.1 min in the control group to 43.8 +/- 4.6 min in the hypomagnesemic swine. In conclusion, magnesium deficiency is associated with prolonged recovery from myocardial stunning.

Animal Feed↗

Sterile mediastinal gas mimicking abscess in aortic aneurysm repair.

Six weeks after aortic aneurysm repair, computed tomography (CT) showed mediastinal gas where absorbable gelatin sponge (Gelfoam) was used. A leukocyte scan labeled with indium 111, however, was normal and surgical exploration showed no infection. Sterile gas collections may be seen following absorbable gelatin sponge use many weeks after surgery and 111In-labeled leukocyte scanning may be a useful differential test.

Abscess↗

Myocardial blood flow during exercise in dogs with left ventricular hypertrophy produced by aortic banding and perinephritic hypertension.

This study tested the hypothesis that for similar degrees of left ventricular hypertrophy, subendocardial blood flow would be facilitated by the increased diastolic coronary perfusion pressure associated with arterial hypertension, as compared with hypertrophy produced by banding the ascending aorta. Left ventricular hypertrophy was produced with perinephritic hypertension in seven adult dogs and by banding the ascending aorta in nine adult dogs. Left ventricular/body weight ratios were 6.15 +/- 0.59 g/kg in the hypertensive animals and 6.87 +/- 0.47 g/kg in dogs with aortic banding, as compared with 4.23 +/- 0.23 g/kg in seven normal dogs (p less than .01). Studies were performed at rest and during two stages of treadmill exercise to achieve heart rates of 195 and 260 beats/min. Diastolic aortic pressure was increased in animals with hypertension but not in dogs with aortic banding. Systolic ejection period was prolonged in dogs with aortic banding but not in hypertensive dogs. Mean blood flow per gram of myocardium measured with microspheres was similar at rest and during light exercise in all three groups of animals, whereas during heavy exercise blood flow was significantly greater than normal in both groups with hypertrophy. In normal dogs subendocardial/subepicardial (endo/epi) flow ratios did not change significantly during exercise. In both groups with hypertrophy, endo/epi ratios were normal at rest but decreased significantly during exercise. During heavy exercise the endo/epi ratio decreased to 0.73 +/- 0.08 in dogs with aortic banding as compared with 1.07 +/- 0.12 in hypertensive dogs (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long term model for evaluation of myocardial metabolic recovery following global ischemia.

Myocardial ATP levels remain depressed following significant periods of ischemia (Isc) despite reperfusion (Rpf). Neither the rate of in vivo ATP return following global Isc nor the factors which influence recovery have been defined. In order to determine the time course to complete the return of ATP levels and evaluate methods of enhancing recovery of ATP levels, we have devised a chronic canine model of global Isc. In this model serial ventricular biopsies can be taken in the awake animal over several days without reoperation which allows an investigation of the recovery of the myocardium following a uniform global insult to be performed. Recovery of ATP levels has been shown to depend, at least in part, on the availability of precursors and the activity of the ATP regenerating enzymes. Because complete recovery of ATP levels takes days, short term (hours) models have limitations. Previous attempts at enhancing ATP recovery following Isc have been only partially successful because either the degree of depression was not great or the period of observation was short, resulting in incomplete return. To identify the best precursor choice, we previously measured the activity of the AMP regenerating enzymes, adenosine kinase (AdK) (adenosine----AMP) and adenine phosphoribosyl transferase (APRT) (adenine----AMP). Because APRT activity was 20 fold higher than AdK with similar Km values for substrates, it appeared that adenine (A) is preferred to adenosine for AMP regeneration in the dog's myocardium. The formation of 5-phosphoribosyl 1-pyrophosphate (PRPP) may also be rate limiting and, therefore, the effect of ribose (R) on ATP recovery was also evaluated. Recovery of ATP levels was assessed in three groups: (1) normal saline (NS), (2) A (20 mM) in normal saline (A/NS) or (3) A with R (80 mM) in normal saline (A/R) were infused (1.0 ml/min) into the right atrium of dogs for 48 hours following Isc. In all groups, ATP levels fell to between 46-60% of pre-Isc levels during Isc. In the NS dogs, ATP levels continued to fall slightly to 46% pre-Isc levels during the first four hours of Rpf after Isc. By 24 hours no appreciable recovery had occurred and the measured ATP was only 51% of the pre-Isc value. Even by seven days, ATP had not returned fully, and by extrapolation, complete recovery required 9.9 +/- 1.4 days. Treated dogs showed, however, that ATP recovery could be significantly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

Myocardial blood flow in left ventricular hypertrophy developing in young and adult dogs.

This study was performed to test the hypothesis that growth of coronary vasculature would be facilitated if myocardial hypertrophy occurred during the period of normal body growth rather than in mature adult animals. Left ventricular hypertrophy was produced by banding the ascending aorta in eight young dogs 7 wk of age and in nine adult dogs. Adult dogs were studied 2 mo after aortic banding, whereas young dogs were allowed to grow to adulthood before study. Left ventricular weight-to-body weight ratios were increased to 6.88 +/- 0.36 g/kg in the young dogs and 6.64 +/- 0.47 in adult dogs; both were significantly greater than seven normal control animals (4.32 +/- 0.05; each P less than 0.01). Myocardial blood flow per gram measured with microspheres during quiet resting conditions was significantly higher in young dogs with left ventricular hypertrophy than in normal dogs. Myocardial blood flow rates during maximum coronary vasodilation with adenosine (4 mumol X kg-1 X min-1 iv) were similar in all three groups. However, since mean coronary perfusion pressure was higher in the dogs with aortic banding, minimum coronary vascular resistance per gram of myocardium was significantly higher in both young (21.1 +/- 3.1 mmHg X ml-1 X min X g) and adult dogs with left ventricular hypertrophy (21.8 +/- 2.2) than in the normal dogs (16.8 +/- 3.1; each P less than 0.01). Mean coronary vascular resistance for the total left ventricle was similar in all three groups of animals, suggesting that growth of coronary vasculature did not occur as the myocardium underwent hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis.

Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventricular:body weight ratio was 7.1 +/- 0.4 as compared to 4.4 +/- 0.3 g/kg in 11 normal dogs (P less than 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 +/- 0.39) was substantially less than in normal dogs (6.19 +/- 0.54 ml/min per g; P less than 0.01), whereas minimum coronary resistance was increased from 14.1 +/- 1.7 in normal dogs to 23.7 +/- 5.4 mmHg. min X g/ml (P less than 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress.

Animals↗

Defining end systole for end-systolic pressure-volume ratio.

The end-systolic pressure-volume (ESPV) ratio (Emax) has recently been accepted as a valid cardiac contractility index. However, in vivo, it is difficult to define end systole (ES) precisely. This study was designed to analyze the effects of eight different ES definitions on Emax. Nine chronically instrumented dogs were studied prior to and during the sequential infusions of phenylephrine (0.2 mg/min), epinephrine (2.0 micrograms/min), and dobutamine (10 micrograms/kg/min). Left ventricular (LV) dimensions and pressure were measured with sonomicrometers and micromanometer. ES was defined at peak LV pressure (PLVP), end-ejection, dp/dt min, 10, 20, 30 msec before dp/dt min, minimum volume before dp/dt min, and left-upper-corner of pressure volume loop (LUC). Although ESPV relationship from each definition was linear (mean r 0.89 +/- 0.3, range 0.76 to 0.99) and sensitive to inotropic changes, the Emax's were not all the same. The r was highest with LUC (mean 0.94 +/- .02, range 0.90 to 0.99) and lowest with PLVP (mean 0.85 +/- 0.03, range 0.76 to 0.92). Emax from PLVP was least sensitive to epinephrine and dobutamine infusions. Thus, in order to compare different values of Emax, the definition of ES must be precise and consistent. Although all the above eight definitions of ES appeared to produce reasonable ESPV relationship, PLVP appeared to be the worst while LUC appeared to be the best ES definition for determining Emax.

Animals↗

Role of the surgeon in the treatment of children's cancer.

The management of children's tumors has changed significantly in the past several years. New techniques and combined surgical, chemotherapeutic, and radiation approaches are responsible for improved survival in most instances. Cooperation of the surgeon with the specialists in separate disciplines is imperative to continued advancements in neoplastic disease of childhood.

Adolescent↗

Global left ventricular contractility in three models of hypertrophy evaluated with Emax.

Using the load independent contractility index, end-systolic pressure-volume ratio (Emax), contractility of the hypertrophied left ventricle (LV) from three different models was evaluated in conscious, resting dogs. The experimental animals included 12 dogs with perinephritic hypertension (HYP) (aortic diastolic pressure 130 +/- 5 mm Hg), 12 dogs who underwent aortic banding (AOB) at 6 to 8 weeks of age (resting aortic gradient 110 +/- 15 mm Hg), and 12 dogs with chronic fluid overload from aortocaval fistula (ACF). These were compared with 12 normal dogs (CTL). LV dimension and pressure were measured with ultrasonic tranducers and micromanometers. All three models resulted in hypertrophy with significant (P less than 0.01) increase in LV weight-to-body weight ratio (6.3 +/- 0.4, 8.4 +/- 0.5, 6.3 +/- 0.4, respectively, vs 4.4 +/- 0.1 g/kg). Cardiac output (6908 +/- 740 vs 2424 +/- 276 ml/min) and end-diastolic volume (118 +/- 11 vs 50 +/- 4 ml) were significantly (P less than 0.01) increased in AOB (18 +/- 1 vs 9 +/- 2 mm Hg). dp/dtmax was not significantly different among all groups. Emax (CTL = 5.3 +/- 0.4 mm Hg/ml) was not significantly changed in HYP (9.5 +/- 2.1) but was significantly (P less than 0.01) increased in AOB (14.1 +/- 2.6), and significantly (P less than 0.01) depressed in ACF (2.4 +/- .03). Thus, LV hypertrophy from systemic hypertension (HYP) or proximal aortic hypertension (AOB) is, at least initially, associated with preservation of contractility and normal hemodynamic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early mechanical function in the heterotopic heart transplant.

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1-12 hr post TX (P1), 12-24 hr post TX (P2), and 24-48 hr post TX (P3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P1) there was significant (P less than 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 +/- 5 vs 80 +/- 10 mm Hg; dp/dtmax, 2642 +/- 170 vs 1038 +/- 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 +/- 0.50 vs 2.41 +/- 0.56; and Emax, 6.5 +/- 1.2 vs 2.0 +/- 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 +/- 0.07 vs 1.37 +/- 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P3: 109 +/- 6 mm Hg, 1842 +/- 450 mm Hg/sec, 5.54 +/- 0.77 cm/sec, and 4.5 +/- 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recovery of adenine nucleotide levels after global myocardial ischemia in dogs.

Loss of myocardial adenosine triphosphate (ATP) during ischemia can result in decreased cardiac function. Postischemic ATP levels remain low, and the reason for this is poorly understood. Previous attempts to enhance ATP recovery after ischemia have been only partially successful. To determine the long-term dynamics of ATP recovery and evaluate the effect of providing ATP precursors, we devised a method of obtaining sequential ventricular biopsies in dogs after 20 minutes of normothermic global ischemia on cardiopulmonary bypass. Our kinetic data show adenine (A) is metabolically favored over adenosine to regenerate ATP levels when adequate ribose (R) is present to produce phosphoribosylpyrophosphate. Therefore A (20 mM) plus R (80 mM) or saline (NS) was infused (1.0 ml X min-1) into the right atrium of dogs for 48 hours after ischemia. During A infusion myocardial tissue A was 0.19 +/- 0.07 nmol X mg-1, arterial A was 18.3 +/- 1.3 microM, coronary sinus A was 11.0 +/- 1.6 microM, and extraction of A by the myocardium was 38% +/- 10%. We found that while the decrease in ATP levels during ischemia was at least 50% in both groups, the postischemic ATP recovery rate in A/R dogs was more than eightfold greater than de novo synthesis (2.8 +/- 0.59 versus 0.34 +/- 0.06 nmoles X mg-1 X day). ATP levels in NS dogs were only 54% +/- 8% of preischemic values by 48 hours and required 9.9 +/- 1.4 days for full recovery. Recovery in A/R dogs required 1.2 +/- 0.2 days. Our results reveal that ATP recovery after a significant ischemic insult is slow, precursor availability is an important limiting factor in ATP recovery, and recovery time can be greatly shortened with precursor infusion even when started after the ischemic insult.

Adenine↗

Left ventricular adaptation to volume overload from large aortocaval fistula.

The manner in which the left ventricle responds to an acute volume overload has not been well defined. Left ventricular performance was studied in six chronically instrumented resting awake dogs in the control state and serially after creation of a large abdominal aortocaval shunt. Ultrasonic transducers measured minor and major axis diameters and equatorial wall thickness. Left ventricular pressure was obtained with micromanometers. Cardiac contractility was evaluated by the load-independent contractility index, EMAXsc (slope of the normalized end-systolic equatorial midwall circumferential stress-equatorial midwall circumference relationship). By 1 week postshunt, the dog had clinical signs of congestive heart failure (ascites, dyspnea, limb edema); although systolic aortic pressure remained stable, heart rate, end-diastolic volume, pulse pressure (systolic minus diastolic pressure), cardiac output, minute work and dp/dtmax were significantly increased. At 1 week the calculated left ventricular mass was increased by 10.1% +/- 4.0% above control. EMAXsc was significantly increased immediately after shunting but returned to control at 1 day and was less than control at 1 week. Thus adaptation of the left ventricle to acute volume overload is characterized by use of inotropic, chronotropic, and Starling reserves. However, chronic volume overload is characterized by decreased inotropic state and an apparent increase in hemodynamic performance (dp/dtmax, cardiac output, minute work), which appears to be maintained by an increase in cardiac mass and by chronotropic and Starling reserves.

Adaptation, Physiological↗