Iv Adenosine Research Articles

SURVIVING THE STORM: USE OF THERAPEUTIC PLASMA EXCHANGE IN THYROID STORM

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Thyroid storm is a severe, life threatening exacerbation of thyrotoxicosis. It is characterized biologically by extremely elevated levels of circulating thyroid hormone and multiorgan dysfunction. Even with treatment, thyroid storm related mortality is 30%, it is mostly associated with cardiac arrhythmias and progressive cardiomyopathy. Initial treatment is aimed at treating the adrenergic symptoms, reducing the thyroid hormone production and peripheral conversion of thyroxine to triiodothyronine. We present a patient with thyroid storm who failed maximal conventional medical management and clinically improved only after multiple sessions of therapeutic plasma exchange (TPE). CASE PRESENTATION: A 60-year-old female with past medical history of Grave's disease presented to the hospital for shortness of breath, palpitations and bilateral lower extremity edema for past 3 days. Patient reported being diagnosed with Grave's disease 2.5 years and noncompliance with her medications. On presentation, she was in atrial fibrillation with rate in 200's, was given 12 mg and 6 mg of intravenous (iv) adenosine and started on iv diltiazem drip. Her Burch - Wartofsky score was 60, indicative of thyroid storm. She was also treated with oral propranolol 60 mg every 6 hours, oral propylthiouracil (PTU) 150 mg every 8 hours and oral prednisone 20 mg every 12 hours. Initial labs revealed TSH: <0.005 UIU/mL, free T3: 26.93 pg/mL, Total T3: >650 ng/dL and Total T4: 24.52 mcg/mL , which improved to free T3: 5.47 pg/mL, free T4: 5.62 ng/dL ,TSH <0.005 UIU/mL and thyroid stimulating immunoglobulin(TSI): 455 after antithyroid medications. Patient failed desynchronized cardioversion for her rapid Atrial fibrillation. She underwent 4 sessions of TPE and she converted to sinus rhythm after the second session. Post TPE, labs revealed free T4: 1.90 ng/dL, free T3: 3.17 pg/mL, suppressed TSH <0.005 UIU/mL. She was discharged on oral PTU and oral prednisone with follow up with the endocrinologist in 2 weeks. DISCUSSION: During TPE, thyroid-binding globulin and bound thyroid hormones are removed with the plasma. Then the colloid replacement (albumin) provides new binding sites for circulating free thyroid hormone. TPE was used successfully in our patient, resulting in a decline of both free T3 and Free T4 and improvement of her symptoms. Given the significant and rapid improvement in our patient, TPE can be considered in the treatment course of thyroid storm when antithyroid medications fail to ameliorate the symptoms. CONCLUSIONS: In severe cases of thyroid storm when conventional medical therapy has failed, TPE should be considered as a treatment option. Reference #1: Plasmapheresis in Thyroid storm, Riham Elmahboubi, MD resident Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, SUN-573, https://doi.org/10.1210/js.2019-SUN-573 DISCLOSURES: No relevant relationships by Anvitha Ankireddypalli, source=Web Response No relevant relationships by Harsh Mehta, source=Web Response No relevant relationships by Praveen Kumar Vikraman, source=Web Response

Abstract 18978: Resting Pressure Gradient (iFG) Instantaneous Wave-free ratio (iFR) for Non-culprit Stenosis Evaluation in Patients with Acute Coronary Syndromes. Preliminary Data from the FORECAST Study

Background: The assessment of non-culprit stenoses is an important issue in ACS. Adenosine administration is currently required for functional evaluation of stenosis severity using the fractional flow reserve (FFR). An alternative adenosine-independent index of coronary stenosis, the instantaneous wave-free ratio (iFR), was recently introduced. Objective: Aim of the present study was to evaluate the trans-stenotic instantaneous wave-free pressure gradient (iFG), the instantaneous wave-free ratio (iFR) and the fractional flow reserve (FFR) in ACS patients. Methods: Intracoronary diastolic pressure was measured proximal and distal to the stenosis during the wave-free period with a pressure wire (Certus, St. Jude, USA) at baseline and upon iv adenosine administration (140 ug/kg/min). The data were acquired with a PowerLab (AD Instruments, USA) and analyzed with a LabChart 7. Results: A total of 71 stenoses were evaluated in the present study. iFR showed a correlation with FFR (r=0.61, p&lt;0.001), while a proportional error was documented with the Bland-Altman analysis. At multivariate analysis, the localization of the evaluated stenosis within the coronary tree influenced the correlation of iFR with FFR (p=0.03). ROC analysis showed a promising diagnostic efficiency for detection of significant coronary stenosis with iFR (AUC=0.936; p&lt;0.001) or iFG (AUC=0.944; p&lt;0.001). Conclusions: The instant wave-free ratio (iFR) and the resting distal-to-proximal pressure gradient measured during the wave-free period (iFG) showed a good diagnostic performance for the assessment of non-culprit lesions in ACS, representing a promising and adenosine-independent alternative to standard fractional flow reserve (FFR).

Myocardial microvascular function during acute coronary artery stenosis: effect of hypertension and hypercholesterolaemia

Coronary collateral arteries (CCA) reduce cardiovascular events. We tested the hypothesis that new microvessels that proliferate in early atherosclerosis may be associated with myocardial protection during acute subtotal coronary artery obstruction (CAO). Acute left anterior descending CAO was induced by a balloon catheter in pigs after 12 weeks of high-cholesterol (HC) diet, renovascular hypertension (HTN), or normal control. Cardiac structure, myocardial perfusion, and functional response to iv adenosine and CAO were studied in vivo using electron beam computed tomography (CT). The intra-myocardial microvessels were subsequently evaluated ex vivo using micro-CT, and myocardial expression of growth factors using immunoblotting. Basal myocardial perfusion and microvascular permeability were similar among the groups, whereas their responses to adenosine were attenuated in HC and HTN. A significant decline in myocardial perfusion in normal pigs during acute CAO was attenuated in HC and abolished in HTN. CAO also elicited an increase in normal anterior wall microvascular permeability (+202 +/- 59%, P < 0.05), which was attenuated in HC and HTN (+55 +/- 9 and +31 +/- 8%, respectively, P < 0.05 vs. normal). Microvascular (<200 microm) spatial density was significantly elevated in HC and HTN, accompanied by increased myocardial growth factor expression. This study demonstrates that early exposure to the cardiovascular risk factors HC and HTN protects the heart from decreases in myocardial perfusion during acute subtotal CAO. This protective effect is associated with and potentially mediated by pre-emptive development of intra-myocardial microvessels that might serve as recruitable CCA.

Abstract 6133: Microvascular Dysfunction and Chronic Inflammation in Patients without Cardiovascular Risk Factors

Premature coronary atherosclerosis, which is actually seen as an active inflammatory process, is an established complication of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We hypothesized that exposure to chronic inflammation, even in the absence of classical cardiovascular risk factors (CVRF), could result in coronary microvascular dysfunction (CMD), an early marker of coronary atherosclerosis. By means of positron emission tomography in combination with oxygen-15 labeled water, myocardial blood flow (MBF) was measured at rest and during iv adenosine infusion (140 μg/kg/min) in 13 SLE and 12 RA patients (mean [±SD] age 44±10 years) without CVRF. All patients underwent coronary angiography using multi-slice (64 slices) computed tomography and only those with none or trivial coronary artery disease (&lt;30% luminal stenosis) were included. A group of 25 age- and gender-matched controls were also studied. There were no differences between patients and controls regarding body-mass index, blood pressure and lipid parameters. RA and SLE patients showed similar mean disease duration (16±11 and 11±7 years, respectively; p=0.12). Resting MBF was similar in patients and controls (1.25±0.27 vs 1.15±0.24 ml/min/g, p=0.15). However, during adenosine stress patients had lower MBF compared with controls (2.94±0.83 vs 4.11±0.84 ml/min/g, p&lt;0.001). As result, coronary flow reserve (CFR; adenosine/resting MBF) was significantly reduced in patients (2.44±0.78) compared with controls (3.81±1.07; p&lt;0.001). Seven patients showed ischemic electrocardiographic changes during adenosine and had a more severe reduction in CFR (1.76±0.81) and more years of disease (21±7 years) compared with those patients without ischemic changes (CFR 2.49±0.54; p=0.006; duration of disease 14±5 years; p=0.03). CFR was inversely correlated with years of disease (r=−0.65, p&lt;0.001), but not with corticosteroid cumulative dose (r=0.20, p=0.39). Chronic inflammation in the absence of traditional CVRF is characterized by severe CMD. This may represent an early marker of disease which precedes and contributes to premature coronary artery disease in patients with RA and SLE.

Abstract 2755: Increased Efficacy of Catheter Ablation Of Atrial Fibrillation by Using Adenosine to Reveal Dormant Pulmonary Vein Conduction

Recurrences of atrial fibrillation (AF) after catheter ablation are frequently associated with recovery of conduction between the pulmonary veins (PV) and the atrium. The recovery of PV conduction could be explained by the presence of dormant conduction between the PV and the atrium. Adenosine can be used during AF ablation procedures to reveal transient re-conduction of the isolated pulmonary vein (dormant PV conduction). We prospectively evaluate the utility of iv adenosine to guide elimination of dormant PV conduction by additional radiofrequency (RF) applications during AF ablation procedures. Thirty-four consecutive patients (30 male; age 51+/−8 years) referred for catheter ablation of drug-refractory AF (Paroxysmal 31/Persistent 3) were studied. Electrical PV isolation (PVI) was performed using Irrigated-tip radiofrequency (RF) ablation and was guided by a circular mapping catheter. After PVI, the presence of dormant conduction in each vein was assessed by injection of 12 mg of adenosine. If dormant conduction was present, additional RF energy was delivered at sites of transient re-conduction. Abolition of the dormant conduction was then demonstrated by repeated injections of adenosine. The recurrence rate of arrhythmia after one procedure was evaluated. The results were compared to an historical control group comprising the previous 34 consecutive patients who underwent PVI without the use of adenosine. Electrical PVI was achieved in 100% of PV’s and all 34 patients underwent the adenosine evaluation. Dormant PV conduction was observed in 17/34 patients and could be eliminated in all by additional RF delivery. Procedural and fluoroscopy times were 163±30 and 49±13 minutes, respectively. After a mean follow-up of 8.0±3.1 months, 6/34 (18%) patients experienced AF recurrence with 28/34 (82%) remaining free of arrhythmia without the use of antiarrhythmic drugs. When compared to the 14/34 patients (41%) from the historical control group who had AF recurrence, a significant reduction was observed (P&lt;0.01). The use of adenosine to guide elimination of dormant PV conduction increases the success rate of AF ablation procedures. This needs to be evaluated in a randomized multicenter trial.

The Effect of Adenosine Triphosphate on Vecuronium-Induced Neuromuscular Block

Continuous IV adenosine triphosphate administration has been used during surgery in the expectation of analgesic and vasodilative effects. Because adenosine triphosphate inhibits neuromuscular transmission, we investigated whether the neuromuscular effect of vecuronium was enhanced by IV adenosine triphosphate in 29 patients randomly given either continuous IV adenosine triphosphate 0.1 mg.kg(-1).min(-1) or 0.9% NaCl when undergoing elective minor surgery. Anesthesia was induced and maintained with propofol. Neuromuscular monitoring was recorded from the adductor pollicis muscle using electromyography with train-of-four stimulation of the ulnar nerve. Vecuronium 25, 30, or 40 microg/kg was given and lag time, onset time, and maximum block were recorded. ED50 and ED95 values for each group were derived from least squares linear regression analysis. ED50 and ED95 values were 29 microg/kg and 44 microg/kg, respectively, for the adenosine triphosphate group and 26 microg/kg and 46 microg/kg, respectively, for the controls. Differences in lag time, onset time, and neuromuscular responses between the two groups were not statistically significant. A significantly larger number of patients in the adenosine triphosphate group showed hypotension (systolic blood pressure <80 mm Hg). Our results demonstrated that adenosine triphosphate 0.1 mg.kg(-1).min(-1) did not enhance the neuromuscular block induced by vecuronium.

938-55 Effect of Residual Infarct Artery Stenosis on Flow Reserve After Reperfusion: Implications for Assessing Myocardial Viability Using Myocardial Contrast Echocardiography

Myocardial contrast echocardiography (MCE) in the presence of pharmacologic vasodilation and a fully patent infarct-related artery has been used to assess myocardial infarct (MI) size during acute post-ischemic reperfusion. Because a stenosis (STN) affects reperfusion dynamics, we hypothesized that the degree of residual infarct artery STN affects MCE measures of myocardial viability. Accordingly, 7 open chest dogs were studied. A flow probe, snare, and variable occluder were placed around the left circumflex artery (LCX), which was then occluded for 3 hr, followed by reflow. MCE imaging with albumin microbubbles commenced before and during iv adenosine (ADN) (0.3 mg/kg/min) at each of 3 LCX patency states during reflow: fully patent, moderate, and severe non-flow-limiting STN. MCE images were digitally processed, and MI was delineated with triphenyl tetrazolium chloride (TIC). TIC-determined MI size was 18 ± 7% of the short-axis slice. Without ADN, MCE defects were smallest with no STN (11 ± 7%, P &lt; 0.01 vs. any STN). intermediate with moderate STN (18 ± 8%), largest with severe STN (19 ± 10%), and most closely approximated MI size when a residual STN was present. With addition of ADN, progressively larger MCE defects occurred, starting with no STN (20 ± 10%), moderate STN (28 ± 10%) and severe STN (36 ± 13%, P &lt; 0.05). With ADN, MCE defects overestimated and were unrelated to MI size in the presence of a severe STN (r = 0.39). slightly overestimated MI with a moderate STN (y = x + 8.02, P &lt; 0.05), and best predicted MI when no residual STN was present (y = x + 0.65, p &lt; 0.01). In conclusion, MCE without pharmacologic vasodilation closely approximates MI size when a STN is present during reflow, because a STN attenuates physiologic post-ischemic hyperemia. However, MCE with pharmacologic vasodilation during reflow through a STN overestimates MI in proportion to the degree of STN, since microvascular reserve in the entire risk bed is impaired. Thus, whereas MCE closely predicts MI size during pharmacologic vasodilation when the infarct artery is fully patent, if the infarct artery is stenotic, MCE best predicts MI size in the absence of pharmacologic vasodilation, particularly if the STN is severe.

Use of adenosine in the management of perioperative arrhythmias in the pediatric cardiac intensive care unit.

To assess the safety, efficacy, and diagnostic usefulness of iv adenosine in treating acute episodes of paroxysmal supraventricular tachycardia in critically ill infants and children with congenital heart disease. A consecutive sample study over a 1-yr period. A six-bed pediatric cardiac ICU at a tertiary care center. Nine consecutive critically ill infants and children with congenital heart disease, either awaiting emergent surgery or in the immediate postoperative period, who had at least one episode of tachyarrhythmia treated with iv adenosine. In children less than 50 kg, adenosine was administered in incremental doses of 100, 200, and 300 micrograms/kg every 3 mins. Patients weighing greater than 50 kg were given doses of 6, 12, and 18 mg iv. The adenosine protocol was stopped when the arrhythmia was terminated or a mechanism of the arrhythmia was shown that would not respond to adenosine administration. Adenosine was used 14 times in nine patients, all of whom were hemodynamically unstable before or after the development of the tachyarrhythmia. Adenosine was effective in rapidly terminating all nine episodes of paroxysmal supraventricular tachycardia, six of which occurred in patients known to have Wolff-Parkinson-White syndrome. All patients had marked hemodynamic improvement after conversion to normal sinus rhythm. In five episodes of tachyarrhythmia that did not respond to adenosine, the transient block at the atrioventricular (A-V) node helped determine the underlying arrhythmia without clinically important side-effects. Adenosine can be used safely and effectively in critically ill infants and children with congenital heart disease and perioperative tachyarrhythmia. More investigation into the "chemical conversion" of paroxysmal supraventricular tachycardias as well as its diagnostic value in this subset of critically ill patients is warranted.

Changes in the rate of formation and resistance to reabsorption of cerebrospinal fluid during deliberate hypotension induced with adenosine or hemorrhage.

Adenosine is recommended for induction of deliberate hypotension. Although its effects on brain vasculature and metabolism and intracranial pressure have been reported, its effects on cerebrospinal fluid dynamics have not. In this study the rate of cerebrospinal fluid formation (Vf), resistance to reabsorption of cerebrospinal fluid (Ra), and electroencephalogram (EEG) activity were determined in rabbits before and during decrease of cerebral perfusion pressure (CPP) with intravenous (iv) adenosine or hemorrhage. In the adenosine group (n = 6), Vf and Ra were determined at control CPP, at CPP of 50, 35, and 28 mmHg achieved with iv adenosine, and at CPP greater than 60 mmHg achieved with iv adenosine combined with iv phenylephrine. In the hemorrhage group (n = 6), Vf and Ra were determined at the first four experimental conditions only. Control values for Vf (9 +/- 3 and 9 +/- 4 microliter.min-1, mean +/- SD) and Ra (428 +/- 567 and 412 +/- 144 cmH2O.ml-1.min) did not differ between groups. In the adenosine group, Vf did not change significantly when CPP was decreased. However, in the hemorrhage group, Vf decreased significantly at CPP of 50 and 35 mmHg and became unmeasurable at CPP of 28 mmHg. Ra did not change significantly in either group. An increase of low-frequency (0.5-3.0 Hz) EEG activity and/or decrease of higher-frequency (3.5-30 Hz) EEG activity occurred at CPP of 28 mmHg in the adenosine group and at CPP of 35 mmHg in the hemorrhage group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic hypertension on vasa vasorum in the thoracic aorta.

The outer layers of the thoracic aorta receive substantial blood flow through vasa vasorum within the aortic wall. Flow delivered via these channels is functionally important because medial necrosis occurs when vasa vasorum are ligated. If flow through vasa vasorum is limited in chronic hypertension, this could contribute to medial necrosis and, perhaps, aortic dissection. In these experiments, flow and conductance in vasa vasorum were assessed in twelve awake dogs with renal hypertension (arterial pressure = 127 +/- 4 mmHg [mean +/- SE]) and nine normotensive controls (arterial pressure = 100 +/- 3 mmHg [P less than 0.001]). At rest, blood flow delivered via vasa vasorum to the thoracic aorta was similar in hypertensive and normotensive dogs (5.2 +/- 0.9 and 4.8 +/- 0.4 ml . min-1 X 100 g-1 respectively). Thus, in hypertensive dogs, conductance of the vasa vasorum decreased to maintain flow constant. During maximal dilatation induced by iv adenosine (4.7 mumol . kg-1 per min) flow delivered via vasa vasorum increased by 100% in both hypertensive and normotensive dogs. Calculations of maximum conductance indicate that vasodilator capacity was decreased by 67% in vasa vasorum of hypertensive dogs. These data suggest that vasodilator capacity of vasa vasorum in the thoracic aorta is limited in chronic hypertension. This abnormality could contribute to the pathogenesis of medial necrosis and aortic dissection in hypertensive patients.

Transmural coronary vasodilator reserve, and flow distribution during tachycardia in conscious young swine with right ventricular hypertrophy.

Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using radionuclide labelled 15 micron diameter microspheres that were injected into the left atrium. It was observed that MBF per unit myocardial mass in the hypertrophied right ventricle (RV) of PAB pigs was similar to that in the RV of normal pigs. Also, minimal coronary vascular resistance per unit myocardial mass was similar between the two groups of pigs for RV as well as left ventricle (LV). This suggests that the increase in RV myocardial mass of young PAB swine was attended by appropriate adjustments in functional cross-sectional area of the RV coronary vascular bed. Despite similarity of maximal coronary vasodilator capacity in the two groups of swine, during pacing induced tachycardia MBF in the hypertrophied RV subendocardium as well as the right and middle layers of the interventricular septum in PAB pigs increased to a significantly lower level than in normal pigs and the RV endo:epi perfusion ratio, unlike in normal pigs, decreased to near unity. Increments in transmural LV MBF of PAB pigs were also attenuated during pacing at 225 and 275 beats X min-1 but the LV endo:epi perfusion ratio for the two groups of pigs remained similar. These findings suggest a possible overall depression of myocardial function in PAB swine.

Regional myocardial blood flow and coronary vascular reserve in unanesthetized ponies during pacing-induced ventricular tachycardia

To examine the effects of tachycardia on coronary circulation, transmural distribution of myocardial blood flow (MBF, 15-μm diameter radionuclide-labeled microspheres) was studied in six healthy adult ponies at rest (heart rate = 60 ± 7 beats · min −1), during ventricular pacing at 150 and 200 beats · min −1, as well as with ventricular pacing at 250 beats · min −1 before and during maximal coronary vasodilatation (iv adenosine infusion; 4 μmole · kg −1 · min −1). Mean aortic pressure and cardiac output were unchanged from control values with ventricular pacing. Whereas ventricular pacing at 150 and 200 beats · min −1 resulted in a progressive uniform increase in transmural MBF and well-maintained endo:epi perfusion ratio, pacing at 250 beats · min −1 did not result in a further increase in MBF compared to pacing at 200 beats · min −1 and the left ventricular (LV) subendocardial:subepicardial (endo:epi) perfusion ratio was significantly less than 1.00 (0.87 ± 0.05). Blood flow to the LV papillary muscles and subendocardium was significantly less than that recorded at 200 beats · min −1. The LV endo:epi perfusion ratio with ventricular pacing at 250 beats · min −1 during adenosine infusion resulted in a decrease in mean aortic pressure (63% of control value) and a marked further reduction in blood flow to the LV papillary muscles as well as the LV subendocardium, while MBF increased dramatically in the LV subepicardium compared to values observed during ventricular pacing at 250 beats · min −1 alone. This resulted in a LV endo:epi perfusion ratio of 0.39 ± 0.09. By contrast, transmural right ventricular (RV) MBF increased significantly and the RV endo:epi perfusion ratio was well maintained. These data demonstrate that coronary vasomotion functions to maintain LV subendocardial blood flow in the pony myocardium at a heart rate of 200 beats · min −1, while at 250 beats · min −1 exhaustion of coronary vasodilator reserve in the deeper layers limits further increase in MBF.

Regional myocardial blood flow and coronary vascular reserve in unanesthetized young calves exposed to a simulated altitude of 3500 m for 8--10 weeks.

We determined regional myocardial blood flow (15-micrometer tracer microspheres) and hemodynamics in nine normal calves, seven calves with right ventricular (RV) hypertrophy induced by pulmonary artery banding (PAB) at sea level, and five calves exposed to simulated high altitude (HA) of 3,500 m (PB = 500 mm Hg) for 8--10 weeks. Progression of RV hypertrophy was very rapid in HA calves. RV weight:body weight ratio of 2.74 +/- 0.20 g/kg at 8--10 weeks of sojourn at HA significantly exceeded that in PAB calves (1.98 +/- 0.11 g/kg) 20 weeks post-banding. All calves were studied unanesthetized at sea level before (control) and during maximal coronary vasodilation (iv adenosine; 4 microM/kg per min). Normal and HA calves were also studied during acute hypoxemia (PaO2: 42 +/- 1 mm Hg) induced by administration of 12--13% O2 + N2 in the inhaled gas. RV myocardial blood flow was significantly increased only in PAB calves, whereas in HA calves it was similar to that in normal calves. Left ventricular (LV) mass and blood flow were identical in three groups of calves. Polycythemia did not occur in HA calves. Minimal coronary vascular resistance per unit weight of the hypertrophied RV was identical to that in the normal RV myocardium. This suggested that, despite very fast progression of RV hypertrophy in HA calves, functional cross-sectional area of the RV coronary vascular bed kept pace with the increase in cardiac mass. Minimal coronary vascular resistance per unit weight of the left ventricular myocardium was also identical in three groups of calves. This suggested that chronic hypoxemia by itself did not cause an increase in the functional cross-sectional area of the LV coronary vascular bed. Acute hypoxemia resulted in a significant increase in myocardial blood flow in all calves, but in HA calves, RV endo:epi perfusion ratio decreased below 1.00. Transmural RV myocardial blood flow and RV systolic pressure in HA calves during acute hypoxemia significantly exceeded that in normal calves.

Effect of volume-overload hypertrophy on the coronary circulation awake dogs.

Inadequate coronary reserve is present in left ventricular hypertrophy secondary to hypertension. Since this abnormality might be due in part to vascular hypertrophy of coronary resistance vessels in response to chronic hypertension, we studied a model of ventricular hypertrophy without hypertension. Volume-overload hypertrophy was produced by creating complete heart block in mongrel dogs; 6 to 7 weeks later the dogs were studied in the awake state. The thirteen dogs with chronic heart block had a 49% increase (P less than 0.05) in left ventricular mass compared with eight control dogs. The major findings in this study were: 1) at rest, coronary blood flow (microsphere technique) per unit weight of left ventricle was not increased in dogs with hypertrophy; and 2) the minimal coronary vascular resistance per unit weight of left ventricle calculated during iv adenosine infusion at a rate that produced maximal vasodilatation was not significantly higher in dogs with left ventricular hypertrophy than in controls (16.4 +/- 1.0 vs 14.7 +/- 1.5 kPa . litre-1 . min . 100 g, respectively). Minimal coronary vascular resistance of the entire left ventricle was significantly less in dogs with hypertrophy than controls (13.0 +/- 0.8 vs 17.3 +/- 1.7 kPa . litre-1 . min, respectively). This data suggests that vascular hypertrophy of coronary resistance vessels related to chronic hypertension may be the cause of the increased minimal coronary vascular resistance seen in dogs with pressure-overload left ventricular hypertrophy.

Effects of short- and long-term left ventricular hypertrophy on coronary circulation.

Although most studies suggest that coronary vasodilator responses are impaired in dogs with cardiac hypertrophy, the factors that contribute to this impairment have not been elucidated. To determine if the duration of hypertrophy was an important determinant, we studied coronary vasodilator responses in awake dogs with two-kidney renal hypertension of 6 wk (n = 11) and 6 mo (n = 8) duration. The dogs with hypertension (6 wk and 6 mo) and left ventricular hypertrophy (LVH) had about a 25% (P less than 0.05) increase in LV mass and mean arterial pressure. During maximal coronary vasodilation induced with 4.7 microM . kg-1 . min-1 iv adenosine, maximal flow was significantly decreased in both groups of hypertensive dogs, and minimal coronary vascular resistance was increased by about 50% (P less than 0.05). Minimal coronary vascular resistance was similar in dogs with 6 wk and 6 mo of hypertension and LVH. These experiments suggest that 1) mild LVH (25% increase in LV mass) can significantly decrease coronary dilator reserve and 2) within the time frame examined (6 wk to 6 mo), the duration of hypertension and LVH does not increase the coronary vascular abnormalities associated with cardiac enlargement.

Reduction of maximal coronary vasodilator capacity in conscious dogs with severe right ventricular hypertrophy.

Right coronary reactive hyperemia and the maximal coronary vasodilator response to adenosine were examined in conscious, normal dogs and dogs with right ventricular (RV) hypertrophy. RV hypertrophy was induced by chronic (5-7 months) pulmonary artery stenosis. With RV hypertrophy, RV weight to body weight ratio rose by 70% (P < 0.001), right coronary artery blood flow (Doppler ultrasonic technique) rose from 17 +/- 1 to 51 +/- 5 ml/min, and RV transmural blood flow (radioactive microsphere technique) increased from 0.78 +/- 0.06 to 1.62 +/- 0.10 ml/min per g, while the RV endocardial:epicardial perfusion ratio decreased from 1.36 +/- 0.04 to 1.0 +/- 0.02. Excess blood flow debt repayment following release of a 15-second right main coronary artery occlusion was attenuated markedly (P < 0.001) to 107 +/- 22% from the normal value of 325 +/- 41%. Maximal coronary vasodilator capacity (to iv adenosine) was reduced in the hypertrophied right ventricle, as reflected by a lower (P < 0.05) level of maximal transmural blood flow and a higher (P < 0.02) level of minimum coronary vascular resistance per gram of hypertrophied right ventricle compared to normal. During maximal coronary vasodilation, the endocardial:epicardial perfusion ratio decreased (P < 0.001) below unity in the hypertrophied right ventricle to a level (0.83 +/- 0.06) significantly lower (P < 0.001) than normal (1.16 +/- 0.03). Thus, the development of severe RV hypertrophy is characterized by an attenuated coronary response to acute ischemia and by a reduction in maximal coronary vasodilator capacity. We conclude that the increase in cardiac mass which results from chronic pulmonary artery stenosis is not accompanied by a proportionate increase in cross-sectional area of coronary vessels supplying the hypertrophied ventricle.

Effect of renal hypertension and left ventricular hypertrophy on the coronary circulation in dogs.

SUMMARY The purpose of this study was to investigate the effects of pressure-induced left ventricular hypertrophy on the coronary circulation. Hypertrophy was induced by single-kidney renal vascular hypertension in 12 dogs. Ventricular mass in the dogs with hypertrophy was about 50% greater than in 11 controls. A third group of six dogs, with a similar amount of left ventricular hypertrophy but normal blood pressure after repair of the renal artery stenosis, also was studied. Total and regional myocardial blood flow was measured with radioactive microspheres at rest, during pacing at a rate of 200 (in the control and hypertensive dogs), and during maximal vasodilation induced with adenosine (4.7 juM/kg x min). Results were as follows. (1) Regional distribution of coronary flow was normal at rest in dogs with hypertension and left ventricular hypertrophy and in dogs with hypertrophy alone. (2) Pacing caused at 16% decrease in the endocardial-epicardial perfusion ratio only in the hypertrophied ventricles of the hypertensive dogs. (3) During maximal coronary vasodilation, the coronary vascular resistance of the entire left ventricle was no different among the three groups: the controls, the hypertensive dogs with left ventricular hypertrophy, and the normotensive dogs with left ventricular hypertrophy (0.14 ± 0.02 SEM, 0.16 ± 0.02, and 0.14 ± 0.02 mm Hg/ml x min, respectively). The use of the minimal coronary vascular resistance measured during maximal vasodilation as an index of the functional cross-sectional area of the coronary bed suggests that the cross-sectional area does not increase with hypertrophy. This failure of the cross-sectional area of the coronary bed to increase commensurate with the degree of hypertrophy is due to an anatomical or architectural alteration of the relationship between the coronary bed and the cardiac muscle and is not due to a functional alteration caused by hypertension alone. Thus, the hypertrophied ventricle may be at greater risk of ischemic injury. CLINICAL SUSPICION of inadequate myocardial perfusion due to pressure-induced hypertrophy of the left ventricle has existed for many years.'" 4 Although several investigators have found that blood flow per unit mass of the myocardium of hypertrophied ventricles is normal, 5 " 8 the decreases in capillary density described in hypertrophied myocardium 9 ''" and preliminary reports suggesting relative endocardial hypoperfusion"' 12 imply that the regional distribution of coronary flow may be abnormal in hypertrophied ventricles and that such ventricles might be at increased risk for ischemic injury. To study possible physiological limitations of the coronary circulation in pressure-induced hypertrophy, we produced single-kidney renal vascular hypertension in mongrel dogs. After left ventricular hypertrophy developed, we assessed regional myocardial perfusion at rest, during pacing, and during maximal vasodilation produced by an iv adenosine infusion. We also studied another group of dogs at rest and during adenosine infusion which had ventricular hypertrophy induced in the same manner but were rendered normotensive by repair of the renal artery stenosis. In this manner we were able to isolate the effects of hypertrophy