Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver.

BACKGROUND: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano-scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been reported to date. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of carbon-based nanomaterials. We hypothesized pulmonary exposure to Ag core AgNP induces a measureable increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and is associated with depressed coronary constrictor and relaxation responses. Secondarily, we addressed the potential contribution of silver ion release on AgNP toxicity. METHODS: Male Sprague-Dawley rats were exposed to 200 µl of 1 mg/ml of 20 nm citrate-capped Ag core AgNP, 0.01, 0.1, 1 mg/ml Silver Acetate (AgAc), or a citrate vehicle by intratracheal (IT) instillation. One and 7 days following IT instillation the lungs were evaluated for inflammation and the presence of silver; serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and coronary artery reactivity were assessed. RESULTS: AgNP instillation resulted in modest pulmonary inflammation with detection of silver in lung tissue and alveolar macrophages, elevation of serum cytokines: G-CSF, MIP-1α, IL-1ß, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17α, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Silver within lung tissue was persistent at 7 days post IT instillation and was associated with an elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. AgAc resulted in a concentration dependent infarct expansion and depressed vascular reactivity without marked pulmonary inflammation or serum cytokine response. CONCLUSIONS: Based on these data, IT instillation of AgNP increases circulating levels of several key cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.

High-fat diet induces Ikkbeta and reduces insulin sensitivity in rats with low running capacity.

Rats bred for a high-capacity to run (HCR) do not develop insulin resistance on a high-fat diet (HFD) vs. those bred for a low-capacity for running (LCR). Recently, a link between obesity and insulin resistance has been established via IKKbeta action and IRS-1 Ser (312/307) phosphorylation. This study measured IkappaBalpha and IRS-1 pSer (307) in mixed gastrocnemius muscle in HCR and LCR rats challenged with a 12-wk HFD. HFD treatment resulted in significantly higher glucose and insulin levels in LCR vs. HCR rats. IkappaBalpha levels, an inverse indicator of IKKbeta activity, were lower in LCR vs. HCR rats maintained on chow diet and were reduced further following HFD in LCR rats only. IRS-1 pSer (307) in the LCR rats increased on the HFD vs. chow. We conclude that differences in glucose tolerance between LCR and HCR rats are at least partly explained by differences in IKKbeta activity and pSer (307) levels.

A carotid stenosis model in canines.

A carotid stenosis model was developed in canines in order to study the effects of systemic blood pressure and hemodilution on cerebrovascular perfusion and metabolism during cardiopulmonary bypass in the setting of significant coexistent inflow stenosis. Under general anesthesia, through a low midline neck incision, the carotid sheath was entered and the carotid artery was isolated and retracted medially. The vertebral artery could be identified posterolaterally. After ligating the vertebral artery with a 00 silk tie, carotid stenosis was created by tying bilateral carotid arteries over an 18-gauge needle using a 00 silk tie. The needle was then removed, leaving a tight stenosis. To determine the degree of stenosis, arteriograms were performed, revealing high-grade lesions of greater than 90% stenosis in the carotid arteries and absence of flow through the vertebral arteries. Cerebral blood flow studies during cardiopulmonary bypass (CPB) were performed, revealing a significant decline. Carotid arteries were harvested at the conclusion of the experiments, revealing tight lesions on direct inspection. The mean gradient measured across stenotic segments was >25 mm Hg. In conclusion, a carotid stenosis model can be created successfully in dogs by ligating the vertebral arteries bilaterally and simply using the shaft of a needle to standardize the lumen size of the carotid arteries. We found the diameter of an 18-gauge needle sufficient to produce stenoses of greater than 90% as evidenced by arteriograms.

Transformation of nonvascular acellular tissue matrices into durable vascular conduits.

BACKGROUND: Prosthetic grafts commonly used for vascular reconstruction are limited to synthetics and cross-linked tissue grafts. Within these devices, graft infections are common, compliance mismatch is significant, and handling qualities are poor. Natural biological tissues that are unfixed have been shown to resist infections and be durable and compliant. A natural biological matrix that could be remodeled appropriately after implantation would be a desirable graft for vascular reconstruction. METHODS: SynerGraft tissue engineering strategies have been used to minimize antigenicity and produce stable unfixed vascular grafts from nonvascular bovine tissues. These grafts have replaced the abdominal aortas of 8 dogs that have been followed for up to 10 months. RESULTS: Early evaluation indicates rapid recellularization by recipient smooth muscle actin positive cells, which become arranged circumferentially, into the media. Arterioles were present in the adventitial areas and endothelial cells were seen to cover lumenal surfaces. After 10 months, grafts were patent and not aneurysmal. CONCLUSIONS: These data indicate that SynerGraft processing of animal tissues is capable of producing stable vascular conduits that exhibit long-term functionality in other species.

Differences in myocardial and peripheral VEGF and KDR levels after acute ischemia.

BACKGROUND: Recent clinical use of vascular endothelial growth factor (VEGF) in the treatment of both myocardial and peripheral ischemia has suggested the possibility of tissue specific coregulation of VEGF and its receptors (eg, kinase domain region [KDR]). The present study was performed to detect the relationship between VEGF and KDR protein levels after acute myocardial and peripheral ischemia. METHODS: Eleven dogs were divided into two groups: peripheral ischemia (n = 6, ligation of major limb arteries) and myocardial ischemia (n = 5, circumflex artery ligation). Muscle biopsy specimens were taken from the perfusion territories of the occluded circumflex artery and limb arteries 3 hours and 6 hours after ligation. Protein levels were determined using Western blot analysis. RESULTS: In myocardium, VEGF levels increased on average eightfold from baseline (p < 0.05) both 3 hours and 6 hours after occlusion, whereas myocardial KDR levels dropped by about 60% at 3 hours and 80% at 6 hours (p < 0.05). With limb ischemia, both VEGF and KDR levels were significantly elevated at 3 hours. CONCLUSIONS: In acute ischemia, regulation of VEGF and KDR may be controlled differently in cardiac and skeletal muscle. Myocardial KDR levels showed a significant decrease from baseline compared with a significant rise with peripheral ischemia.

Minimally invasive cardiac operation: adapting cardioprotective strategies.

BACKGROUND: Minimally invasive heart operation differs from traditional cardiac operations through the omission of a sternotomy, cardiopulmonary bypass, or both. Current concerns with minimally invasive operation include: operative safety, learning curve, operative times, arrest times, and adequacy of myocardial protection. While many of the protective strategies used for traditional procedures may be applied to minimally invasive cardiac operations, the safe applications of minimally invasive operations require unique techniques of myocardial protection. METHODS AND RESULTS: Omission of extracorporeal perfusion may benefit patients through attenuation of systemic inflammatory response, decrement in neurologic insults, and reduced bleeding complications. As a counterbalance, surgeons must consider long-term operative quality and level of myocardial protection provided during beating heart coronary operation. Current issues that must be addressed include: pharmacologic management, coronary collateralization and ischemic preconditioning, the utility of intraluminal coronary shunts, and technical adequacy of the anastomosis. Nonsternotomy cardiopulmonary bypass methods utilize alternative incisions and "port-access" technology, and may render more rapid patient recovery including: decreased pain, shortened hospital stay, and more rapid return to work. Altered strategies of myocardial protection in a closed chest environment must address: method of cannulation, technique of aortic occlusion, rapidity and maintenance of cardiac arrest, and cardiac de-airing techniques. CONCLUSIONS: Previous obstacles to minimally invasive cardiac operations included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. Recent advances in videoscopic visualization and evolving mechanisms of myocardial protection may justify the expanding application of minimally invasive techniques.

Regional left ventricular systolic function in humans during off-pump coronary bypass surgery.

BACKGROUND: Controversy exists as to whether off-pump CABG with local occlusion results in clinically significant myocardial ischemia during the occlusion period. This study was undertaken to delineate the effects of transient local coronary artery occlusion on regional systolic function. METHODS AND RESULTS: Eight consenting patients undergoing left internal mammary to left anterior descending coronary artery (LAD) bypass were instrumented with a left ventricular pressure catheter and 2 subepicardial cylindrical ultrasonic dimension transducers placed in the minor axis dimension in the region served by the LAD. A digital sonomicrometer was used to collect data before, during, and after coronary occlusion from which percent systolic shortening and pressure-dimension loops were derived. Measuring devices were removed immediately after the final time point. All patients tolerated the procedure well, and there were no complications. Average duration of local occlusion needed for CABG was 15.9+/-4.4 minutes (range, 12 to 26 minutes). Local occlusion was associated with a decrease in peak systolic shortening from 5.8+/-0.8% to 1.8+/-0.8%. In all cases, function returned to baseline after restoration of flow. Pressure-dimension loops confirmed these findings and no evidence of diastolic creep. Linear repression analysis of degree of stenosis versus change in segmental shortening revealed a significant inverse correlation. CONCLUSIONS: Local occlusion of the LAD resulted in a transient decrease in myocardial function during occlusion with complete recovery during reperfusion. This change was less significant with increasing degrees of coronary stenosis. These data suggest that local occlusion is not associated with permanent myocardial injury but that ischemic changes do occur that may be clinically significant, especially in patients with lesser degrees of coronary stenosis.

A paradox of cerebral hyperperfusion in the face of cerebral hypotension: the effect of perfusion pressure on cerebral blood flow and metabolism during normothermic cardiopulmonary bypass.

BACKGROUND: The purpose of this study was to determine the impact of perfusion pressure on cerebral blood flow (CBF) and metabolism during normothermic cardiopulmonary bypass (CPB) and after weaning. MATERIALS AND METHODS: Two groups of mongrel dogs were studied (Group A, CPB perfusion at 50 mm Hg, n = 6; and Group B, CPB perfusion at 100 mm Hg, n = 6). All animals underwent 2 h of normothermic bypass at cardiac indexes >2.1 L/min/m2 and were weaned from pump, maintained at pressures >75 mm Hg, and followed for an additional 2 h. RESULTS: In both groups CBF increased over 85% from baseline, in proportion to the hemodilution during the initiation of CPB. Intracranial pressure increased moderately in both groups during CPB, compromising CBF at 1 h in Group A, but not in Group B. The Group A cerebral metabolic rate for oxygen (CMRO2), however, remained unchanged as the percentage of oxygen extraction increased to compensate for the decreased CBF. During recovery, temperature, mean arterial pressure, and cerebral perfusion pressure were not significantly different between the two groups. However, the CBF, percentage of oxygen extracted, and CMRO2 were significantly lower in Group A. CONCLUSIONS: Normothermic CPB initiated with a crystalloid prime and performed at the lower end of a 50-70 mm Hg perfusion window resulted in a highly significant increase in CBF in order to compensate for hemodilution, while at the same time reduced the perfusion pressure available to supply the increased CBF. Together, these two events create a hemodynamic paradox of hyperperfusion in the face of hypotension. The reduction in CMRO2 in Group A is yet to be explained but seems to remain coupled to CBF and could represent a previously undescribed protective mechanism of hibernating cerebral tissue, similar to the phenomena of ischemic preconditioning in the heart, where cerebral tissue is stimulated to lower metabolism in response to inadequate CBF.

Video-assisted minimally invasive mitral valve surgery.

OBJECTIVE: This study was done to determine the potential benefits of minimally invasive mitral surgery performed with intraoperative video assistance. METHODS: From May 1996 until March 1997, a minithoracotomy and video assistance were used in 31 consecutive patients undergoing mitral repair (n = 20) and replacement (n = 11). Their ages ranged from 18 to 77 years (59 +/- 2.6 years; mean +/- standard error of the mean). Ejection fractions were 35% to 62% (55% +/- 1.5%). Operations were done with either antegrade/retrograde (n = 10) or antegrade (n = 19) cold blood cardioplegia and a new transthoracic crossclamp or with ventricular fibrillation (n = 2). Peripheral arterial cannulation (n = 28) and pump-assisted right atrial drainage (n = 26) were used most often. RESULTS: No hospital deaths occurred, but the 30-day mortality was 3.2%. Complications included deep venous thrombosis and a phrenic nerve palsy in one patient each. No patient had a stroke or required reoperation for bleeding. Postoperative echocardiography showed excellent valve function in all but one patient. Cardiopulmonary bypass and arrest times averaged 183 +/- 7.2 and 136 +/- 5.5 minutes, respectively. Compared with 100 patients having conventional mitral valve operations, these patients had significantly shorter hospitalization times (8.6 +/- 0.5 vs 5.1 +/- 0.9 days, p = 0.05). Moreover, 81% of the later cohort were discharged between day 3 and 5 (3.6 +/- 0.2 days). Hospital charges (decreases 27%, p = 0.05) and costs (decreases 34%, p < 0.05) were less than in conventional operations. Patient follow-up suggested minimal perioperative pain and rapid recovery. CONCLUSIONS: Early results suggest that video-assisted minimally invasive mitral operations can be done safely. These methods may benefit patients through less morbidity, earlier discharge, and lower cost.

Successful small diameter arterial grafting using cryopreserved allograft arteries.

Intimal hyperplasia (IH) limits the long-term success of veins as arterial grafts. IH occurs in veins partly as an adaptive process to arterial pressure conditions. The authors have previously reported early success with cryopreserved (CP) saphenous veins as aortocoronary bypass grafts, and they have hypothesized that CP arterial segments were already structurally adapted for arterial conditions. Six femoral arterial segments were harvested from three adult donor dogs, and cryopreserved. The segments were thawed and implanted into six recipient dogs, in end-to-end fashion, as interpositional grafts in the femoral artery. A similar length of native femoral artery was removed from the implant site and grafted in the contralateral femoral artery of the same animal to serve as native autograft-matched controls. Grafts were harvested bilaterally after 2 (n = 3) and 4 weeks (n = 3), perfusion fixed (80 mmHg, 15 min), and analyzed histologically. All grafts were patent at harvest, and flows distal to the grafted segments were not significantly different between grafts within an animal either at implant or subsequent harvest. Although CP arterial grafts still showed slight but significant dilation compared with native autograft, the dilation was much less than seen previously with either CP or native venous segments. No evidence of inflammation or IH was seen in CP arterial grafts. The absence of early IH or inflammation suggests that CP small diameter arteries may perform better than many currently available allograft tissues and synthetic prosthetics.

The temporal expression of transforming growth factor-beta 1 in early aortocoronary vein grafts.

The success of coronary reconstructive procedures is limited by the high incidence of restenosis secondary to intimal hyperplasia (IH). Transforming growth factor-beta 1 (TGF-beta 1) is a growth factor which has been shown to be important in the early development of IH in arteries and peripheral vein grafts. To date, there is little information concerning the early remodeling in aortocoronary vein grafts (ACVG). The purpose of this study was to characterize the expression of TGF-beta 1 expression in early aortocoronary vein grafts. Eighteen mongrel dogs underwent aortocoronary vein bypass grafting. Vein grafts were excised at 2 hr, 4 hr, and 7 days after implantation, snap frozen, and processed for ribonuclease protection assays (RPA) using 32P-labeled riboprobes for TGF-beta 1 and 18 S rRNA. TGF-beta 1 expression was quantified by densitometric analysis of autoradiographs which were expressed as a ratio TGF-beta 1/rRNA. Representative vessel rings were also collected for histology. There was a significant rise in TGF-beta 1 expression in the 2-hr vein grafts (0.42 +/- 0.04 compared to control saphenous vein (0.21 +/- 0.05, P < 0.02). In addition, there was significant downregulation of TGF-beta 1 at 4 hr (0.28 +/- 0.05) and at 7 days (0.18 +/- 0.01) when compared to 2 hr (P < 0.05). Histological specimens showed minimal intimal hyperplasia at 7 days. These results show for the first time an acute rise in TGF-beta 1 expression in ACVG. This upregulation quickly subsides by 4 hr and gene expression approaches control values by 7 days. By understanding this temporal relationship of expression one could better target potential therapeutic modalities to attenuate IH.

In-line leukocyte filtration during bypass. Clinical results from a randomized prospective trial.

Leukocyte mediated pulmonary injury may delay recovery after cardiac surgery, and leukocyte depletion during bypass has been suggested. Two groups of patients were randomly, prospectively assigned from 50 sequential patients to undergo open heart surgery using cardiopulmonary bypass, either with (n = 25) or without (n = 25) leukocyte filters. The two groups were not significantly different regarding age, gender, race, pre-operative ejection fraction, pump time, or cross-clamp time. Post operative arterial blood gases (pO2: 173 +/- 66 vs 192 +/- 107; pCO2: 30.2 +/- 8.2 vs 30.8 +/- 8.0), pulmonary vascular resistance (PVR 105 +/- 45 vs 112 +/- 50 dyne cm-5), time on ventilator (17.8 +/- 6.4 vs 19.7 +/- 8.6 hr), and length of hospital stay (7.65 +/- 4.57 vs 8.52 +/- 5.87 days) were not different between groups (mean +/- SD, with vs without filters, respectively). Arterial oxygenation was somewhat poorer, and PVR was somewhat lower in the leukocyte filtered group. However, these trends did not produce significant decreases in total ventilator time or length of hospital stay. In-line filtration did remove leukocytes, but did not reduce circulating leukocyte count. In effect, leukocyte filtration produced an effective leukocyte concentration at the filter site. These data do not support routine incorporation of in-line leukocyte filtration during bypass.

Extracardiac adjustment of mitral chordae replacement.

This study was designed to determine the feasibility of completing mitral chord repair externally when the heart was weaned from bypass. Ten anesthetized dogs (22.9 +/- 4.6 kg) were placed on cardiopulmonary bypass through a left thoracotomy. The left atrium was opened and one or two marginal chords of the anterior mitral leaflet were divided. A double-armed 2-O polypropylene suture was placed in the margin of the mitral leaflet, and both suture ends were brought outside of the ventricle through the anterior papillary muscle, but were not anchored. Production of mitral incompetence was verified when the animals were weaned from bypass. Mean left atrial pressure (LAPm), the v wave of the left atrial pressure (LAPv), systolic billowing of the anterior leaflet into the left atrium above the mitral closure line (two-dimensional echocardiography, long axis), and function curves (left atrial-aortic systolic pressure, LAPv-AoSP) were used to determine valve competence and functionality of the repair. All values are expressed as means +/- SE. Acute mitral incompetence in this model was associated with severe left atrial bulging, left atrial billowing of the anterior leaflet (7-12 mm, 9.6 +/- 1.6 mm), significantly increased left atrial pressure [LAPv, 30.5 +/- 5.8; LAPm, 23.6 +/- 4.3 mm Hg; both P < 0.01 vs control (10.5 +/- 2.5 and 7.5 +/- 2.7 mm Hg, respectively)], and decreased systemic pressure development (AoSP, 84 +/- 8.8 vs 108 +/- 12.3 mm Hg; P < 0.01). The slope of the atrial-systemic pressure curve was decreased significantly, shifted to the right and reduced by more than half (2.1069 vs 0.9190; P < 0.05). External adjustment of the pledgeted suture ends returned all values to within control limits (LAPv, 12.7 +/- 4.1; LAPm, 9.8 +/- 4.3; AoSP, 104 +/- 10.5; LAP-AoSP slope, 2.0909; all P = n.s.), atrial bulging was not evident, and atrial displacement of the valve leaflet could no longer be visualized. These data suggest that mitral chord repair is feasible through a thoracotomy and, more importantly, final adjustments to obtain optimal chord length can be completed externally, guided by changes in dynamic, physiologic parameters.

Complex valve operations: antegrade versus retrograde cardioplegia?

BACKGROUND: Increasingly complex cardiac procedures demand optimal myocardial protective techniques during the requisite interval of aortic cross-clamping. For complex procedures in which prolonged cross-clamp times are anticipated, we favor combined antegrade and retrograde cold blood cardioplegia. Advantages include rapid arrest, uniform distribution, and an uninterrupted operation. METHODS: We retrospectively evaluated the cases of 194 consecutive patients who underwent complex cardiovascular procedures between January 1988 and October 1994. Procedures performed included valve repair and coronary artery bypass grafting (23.7%), valve replacement and coronary artery bypass grafting (19.1%), complex aortic arch and valve procedures (16.6%), valve repair only (16.5%), reoperative valve (9.8%), and multiple-valve replacements (9.3%). Cardioplegic arrest times averaged 113 +/- 38.5 minutes (range, 52 to 292 minutes). RESULTS: Postoperative left and right ventricular function was evaluated using transesophageal echocardiography. The echocardiograms revealed a 3.1% incidence of new left ventricular dysfunction and no case of right ventricular dysfunction. Of the patients evaluated, 75.7% required little (< 3 micrograms.kg-1.min-1 of dopamine hydrochloride) or no inotropic support postoperatively. The 30-day mortality rate was 3.1%, and no death was due to cardiac failure. CONCLUSIONS: We conclude that myocardial protection using a combined antegrade and retrograde cardioplegia technique permits excellent myocardial protection during complex cardiovascular procedures requiring long arrest times.

Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.

The ability of allopurinol to protect against reperfusion injury in the heart has usually been attributed to its xanthine oxidase (XO)-inhibiting properties. Human myocardium however, has exhibited low levels of XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreatment is necessary, 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left circumflex for 8 minutes followed by reperfusion for 4 hours. One group received allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricular and aortic pressure, electrocardiograms, and regional wall motion (sonomicrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before, during, and 5, 10, and 30 minutes after ischemia. Occlusion decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10 mL/minute/g). The allopurinol-treated group exhibited a mild, generalized hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mL/min/g, which returned to control levels at 10 and 30 minutes. In contrast, the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 versus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 and 30 minutes. When evaluated for the propensity of arrhythmias using an arbitrary arrhythmia score, the allopurinol group demonstrated no myocardial ectopy when compared with the focal ectopy routinely encountered in the control group at all time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cocaine on left ventricular function. Relation to increased wall stress and persistence after treatment.

BACKGROUND: To determine whether alterations in left ventricular (LV) function after a cocaine infusion are due to reduced myocardial contractility or changes in loading conditions, we examined LV function in 30 morphine-sedated, closed-chest dogs. We also wanted to determine the time course of the effects of cocaine on LV function after the infusion was stopped. METHODS AND RESULTS: Two-dimensional echocardiography and hemodynamics provided LV fractional shortening and end-systolic wall stress data. Radionuclide ventriculography was also performed. Four groups of dogs received saline or cocaine infusions of 10, 30, or 100 micrograms.kg-1.min-1. Cocaine was infused for 90 minutes with ECG and arterial pressure monitoring. Animals were monitored for an additional 120 minutes after the infusion ended. Arterial pressure rose over the course of the experiment in all four groups, but saline and cocaine 10 micrograms.kg-1.min-1 did not significantly change ejection fraction. Cocaine 30 and 100 micrograms.kg-1.min-1 acutely increased arterial pressure and heart rate but decreased ejection fraction from 0.64 +/- 0.06 to 0.45 +/- 0.08 and from 0.65 +/- 0.10 to 0.46 +/- 0.11, respectively. Additionally, cocaine 100 micrograms.kg-1.min-1 decreased fractional shortening from 36 +/- 9% to 23 +/- 12%. However, cocaine 30 and 100 micrograms.kg-1.min-1 also increased wall stress from 42 +/- 15 to 65 +/- 11 g/cm2 and from 37 +/- 15 to 90 +/- 33 g/cm2, respectively. These results were analyzed by use of the relation between wall stress and fractional shortening as an index of contractility. Fractional shortening after cocaine infusion was displaced downward as a result of increased wall stress rather than changes in contractility. In addition, alteration of afterload with phenylephrine (6 micrograms/kg) and sodium nitroprusside (10 micrograms/kg) before and during infusion of cocaine 100 micrograms.kg-1.min-1 showed similar regression lines for wall stress to fractional shortening. CONCLUSIONS: Ejection-phase indexes of LV function were reduced by cocaine in this model of conscious, sedated dogs, but effects were attributable to increased wall stress rather than to reduced myocardial contractility. These effects persisted for at least 2 hours after the infusion was stopped.

Experimental supplemental vein grafting and hypoperfusion syndrome.

An additional saphenous vein graft (SVG) sometimes is required to the same coronary system if acute internal thoracic artery (ITA) graft flow is inadequate. These experiments were conducted to determine the consequences produced by ITA-SVG dual grafting. Fourteen dogs each received two coronary grafts (without bypass, using local occlusion) to the proximal circumflex coronary artery, using the ITA and an SVG, and then the circumflex artery was ligated proximally. Simultaneous flow in both grafts was determined at rest and after pharmacologic (adenosine, phenylephrine) or physiologic (cardiac pacing) stimulation. Serial angiography was performed during the first 4 weeks after grafting to determine patency patterns of the ITAs and SVGs. In the resting heart, flow was 7.5 +/- 1.6 mL/min (17.5%) in the ITA graft and 35.3 +/- 5.2 mL/min (82.5%) in the SVG (mean +/- standard deviation [% total distal perfusion]), and the combined flow was not significantly different from the original native flow. Intravenous adenosine (0.2 mg.kg-1.min-1) preferentially increased both the total ITA flow and its fractional contribution to total distal perfusion (18.4 +/- 3.2 [31.1%]; p < 0.05 versus rest). Saphenous vein graft flow was not changed significantly (40.3 +/- 6.0 mL/min), in part due to a modest decrease in arterial pressure. In contrast, intravenous phenylephrine (0.003 mg.kg-1.min-1) decreased both absolute ITA flow and its relative contribution to distal perfusion (6.1 +/- 1.1 [10.9%]; p < 0.05 versus rest), despite an increased systemic perfusion pressure, which increased SVG flow significantly (50.1 +/- 4.8 [89.1%]; p < 0.05 versus rest).(ABSTRACT TRUNCATED AT 250 WORDS)

Distal flow determinants in canine myocardium perfused through internal thoracic artery bypass grafts.

The dynamic reactivity and the acute, recruitable flow capacity of an internal thoracic artery (ITA) graft remains unclear. These experiments were conducted in 20 anesthetized dogs with the left ITA grafted to the circumflex artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle, including anterior descending artery and circumflex regions, totally dependent on the ITA graft. When the left main coronary artery was occluded, the ITA flow immediately increased more than fivefold (93.4 +/- 9.6 mL/min; mean +/- standard deviation), representing an absolute flow value three times higher than ITA flow measured in situ on the chest wall (27.5 +/- 9.6 mL/min; p < 0.05 versus control), and the ITA graft provided total resting flow requirements (93.4 +/- 9.6 mL/min) for both left anterior descending and circumflex coronary artery perfusion territories at levels comparable with measured native flow values (y = (0.9555)x + 21.9272; r = 0.976; p < 0.05). Pharmacologic challenge with adenosine (0.2 mg.kg-1.min-1 intravenously) significantly increased the graft flow (120.3 +/- 18.7 mL/min; p < 0.05 versus control), but also significantly decreased the mean arterial pressure (85.4 +/- 5.0 versus 74.6 +/- 6.1 mm Hg; p < 0.05). Phenylephrine (0.003 mg.kg-1.min-1 intravenously) significantly decreased ITA graft flow (81.2 +/- 9.0 mL/min; p < 0.05 versus control) despite significantly increased perfusion pressure (84.8 +/- 6.3 versus 108.2 +/- 8.6 mm Hg; p < 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac pacing induced flow responses in internal thoracic artery and saphenous vein coronary artery bypass grafts.

The flow reactivity of an internal thoracic artery (ITA) graft and a vein graft for multiple coronary beds in response to different modes of cardiac pacing remains unclear. These experiments were conducted in 14 anesthetized dogs with the ITA or the vein grafted to the circumflex coronary artery, off pump, using a brief local occlusion. The left main coronary artery was occluded, rendering the entire left ventricle totally dependent upon the ITA graft or the vein graft. When the left main coronary artery was occluded and the heart rate was 120 beats per min, graft flow was 93.4 +/- 9.6 ml per min in the ITA, and 96.1 +/- 10.4 ml per min in the vein graft. Atrial pacing to increase heart rates 25% to 150 beats per min increased both the ITA graft flow (110.3 +/- 9.7 ml per min, p < 0.05 versus flow in sinus rhythm) and the vein graft flow (109.8 +/- 7.9 ml per min, p < 0.05 versus flow in sinus rhythm). The increases in flow in both cases were not attributable to changes in perfusion pressure. In contrast, ventricular pacing to the same heart rate decreased systemic pressure slightly, but insignificantly. Despite the slight decrease in perfusion pressure, ventricular pacing increased ITA flow (107.9 +/- 8.4 ml per min, p < 0.05 versus flow in sinus rhythm), but the increase in vein graft flow was not significant compared with flow in sinus rhythm (102.1 +/- 7.3 ml per min, p = ns versus flow in sinus rhythm).(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral vs single internal thoracic artery grafting for left main coronary artery occlusion.

This study was conducted to compare the coronary flow distributed by single and bilateral internal thoracic artery (ITA) grafts in the setting of the left main coronary occlusion. Ten dogs underwent coronary artery bypass grafting through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Dogs were randomly assigned to receive either a single left ITA (LITA) graft to the circumflex coronary artery (CFX), or bilateral ITA grafts, with additional placement of the right ITA (RITA) to the left anterior descending artery (LAD). After the grafts were placed, the left main coronary artery was ligated. Electromagnetic flows were obtained in the LAD and the CFX proximally and distally to ITA grafts in both groups before grafting and after grafting. ITA flow in situ was also measured before rotation from the chest wall. Total left ventricular flow requirements were satisfied equally well by either a single LITA graft (116.7 +/- 11.6 mL/min) or bilateral ITA grafts (total, 116.8 +/- 9.6 mL/min divided as LITA, 55.9 +/- 7.4 mL/min; RITA, 60.9 +/- 12.0 mL/min). When two grafts were replaced, competitive flow in the proximal regions of both native vessels was noted, although basal flow requirements were maintained. When an individual graft was occluded in the bilaterally grafted system, the remaining graft immediately recruited the additional flow, demonstrating that either right or left ITA can support flow demands five to six times higher than in situ chest wall flow (RITA, 21.9 +/- 3.1 mL/min; LITA, 22.3 +/- 4.9 mL/min). These data suggest that in this canine model, a single ITA graft can support the entire flow requirements of the left ventricle. Assuming no intervening stenosis is present in native coronary systems, bilateral ITA grafting may provide a margin of safety, but under resting conditions, provides no perfusion advantages over a single ITA graft.