The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence.

BACKGROUND: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens and young adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitro and in vivo studies have evidenced a variable quantity of potentially harmful components and some recognized carcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes may play active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapid review aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentially malignant disorders (OPMD) and oral cancer. MATERIAL AND METHODS: A systematic search for English language articles published was performed in PubMed (MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelve clinical studies about OPMD and oral cancer risk in e-cigarette users. RESULTS: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes, DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However, results were inconsistent compared to tobacco smokers and control groups. CONCLUSIONS: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes as a risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsibly about the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designed clinical studies are needed.

Clinical manifestations of head and neck cancer in pediatric patients, an analysis of 253 cases in a single Brazilian center.

BACKGROUND: Pediatric head and neck cancer (PHNC) is rare and its nonspecific clinical manifestations may often lead to delayed diagnosis. We aimed to describe the signs, symptoms, and clinicopathological characteristics of PHNC. MATERIAL AND METHODS: Medical records were retrospectively reviewed for all PHNC cases diagnosed from 1986 to 2016 affecting patients aged 19-years and younger from a tertiary referral center in Brazil. Demographic variables, anatomical site of primary tumors, histopathological diagnoses, signs and symptoms, and patterns of misdiagnosis were collected and interpreted by statistical and descriptive analysis. RESULTS: A total of 253 PHNC cases were included. The mean age was 9.3 years and male patients were more frequently affected (60.9%). Burkitt lymphoma (23.7%), nasopharyngeal carcinoma (15.8%), and rhabdomyosarcoma (15.4%) were the most common cancer types. The nasopharynx (28.9%), cervical/lymph node region (25.3%), and craniofacial bones (8.3%) were the predominant anatomical sites. Tumor/swelling (68.4%), was the clinical finding often presented. The univariable analysis showed association between tumor histology and clinical variables such as sex (p=0.022), age (p<0.0001), anatomical location (p<0.0001) tumor/swelling (p=0.034), pain (p=0.031), systemic/general manifestations (p=0.004), nasal/breathing alterations (p=0.012), orbital/ocular alterations (p<0.0001). Misdiagnosis such as tonsillitis, otitis, and abscess were frequent. CONCLUSIONS: Although the clinical findings of PHNC are often unspecific, this study provided signs and symptoms with significant correlations between tumor histology. The suspicion of malignancy should be considered when the main signs and symptoms reported here appear and persist, in order to conduct a timely diagnosis.

Characterization of the functional border zone around regionally ischemic myocardium using circumferential flow-function maps.

Previous studies have suggested that there exists a functional border zone in myocardium at the lateral margins of an ischemic area. The functional border zone is normally perfused but is characterized by abnormal contractile function. To define the spatial characteristics of this border zone, circumferential maps of left ventricular function by two-dimensional echocardiography and of coronary flow using radioactive microspheres were generated in 18 dogs at baseline and after circumflex coronary occlusion. Circumferential left ventricular wall thickening was measured in all dogs at 22.5 degrees intervals over 360 degrees. In seven dogs, the pathologic slice corresponding to the two-dimensional echocardiographic image was circumferentially dissected into 16 segments corresponding to 22.5 degrees intervals and a subendocardial myocardial blood flow map was derived. In the other 11 dogs, autoradiography was performed of the pathologic slice corresponding to the two-dimensional echocardiographic image, and the hypoperfusion zone was directly measured. There was no difference between the circumferential extent of hypoperfusion zones by either perfusion measurement technique in the five dogs that had both techniques performed (140 +/- 12 versus 124 +/- 7 degrees, p = NS). The hypofunctional zone by two-dimensional echocardiography was significantly larger than the hypoperfusion zone (174 +/- 4 versus 125 +/- 26 degrees, p less than 0.0005), indicating that a zone of normally perfused but abnormally contracting muscle surrounds the ischemic area. However, this border zone in our model was small, measuring 49 +/- 34 degrees (approximately 8 to 9 mm on either lateral border). This suggests that the functional border zone lateral to ischemic myocardium exists, but is relatively discrete.

Augmentation of regional function in nonischemic myocardium during coronary occlusion measured with two-dimensional echocardiography.

Increased regional left ventricular function frequently occurs in the nonischemic myocardium after acute coronary occlusion. To further define the regional and global effects of this increased remote function in the ischemic left ventricle, 22 dogs were studied with two-dimensional echocardiography before and 1 h after left circumflex coronary artery occlusion. Two groups of dogs were identified with and without compensatory increased regional left ventricular function, defined as regional wall thickening in the nonischemic zone greater than 2 SD above baseline. After coronary occlusion, nonischemic wall thickening was 76 +/- 15% in the hyperfunction group (n = 11) and 45 +/- 14% in the nonhyperfunction group (n = 11) (p less than 0.001). Despite similar left ventricular end-diastolic cavity areas and equivalent degrees of ischemic wall thinning, dogs with increased left ventricular function in the nonischemic myocardium had a smaller extent of circumferential left ventricular dysfunction (136 +/- 33 versus 170 +/- 43 degrees, p less than 0.001) and a higher area ejection fraction (38 +/- 9% versus 27 +/- 6%, p less than 0.001). These functional differences occurred despite similar myocardial areas at risk by autoradiography (41 +/- 6% versus 37 +/- 12%, p = NS). The data suggest that increased left ventricular function in the nonischemic myocardium determines the global functional impact of acute coronary occlusion and, through interaction with adjacent myocardium, modifies the extent of circumferential left ventricular dysfunction.

Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty.

OBJECTIVES: The study was performed to test the hypothesis that high local, intramural concentrations of antineoplastic agents at the site of balloon injury inhibit vascular smooth muscle cell proliferation without systemic toxicity. BACKGROUND: The predominant mechanism for recurrent stenosis after coronary balloon angioplasty is neointimal thickening due to medial smooth muscle cell proliferation. The clinical use of potent antiproliferative agents to prevent restenosis has been limited by the potential for severe systemic side effects. Local therapy with these agents may be effective and free of systemic complications. METHODS: After bilateral balloon angioplasty of the carotid arteries of 14 juvenile farm pigs, the dilated arterial segments were treated locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution through a perforated balloon catheter. The animals were then killed 30 days after balloon injury to determine the effects of this therapy on neointimal thickness. In an additional six animals, tritium-labeled methotrexate was used to determine the concentration and duration of detectability of methotrexate in the wall of the treated arteries and in the systemic circulation. RESULTS: Two hours after drug instillation the concentration of labeled drug was greater than 1,000-fold greater in the wall of the treated artery than in circulating blood, and this ratio remained between 50 and 100 for at least 7 days. Despite this difference, the mean intimal thickness 30 days after the procedure was similar in the 10 methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs. 56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was similar in each group and suggested an important role for mural thrombus in the genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural methotrexate, delivered through a perforated balloon catheter at the selected concentration and total dose, failed to prevent intimal thickening after balloon injury. Nonetheless, the perforated balloon catheter appears to be a promising means of delivering a high local concentration of drugs with potentially life-threatening systemic side effects. The optimal concentrations and combinations of candidate drug therapies warrant further evaluation.

A reversible pulmonary artery band: preliminary experience.

Pulmonary artery banding has become an infrequently used surgical technique. However, if a band was developed that could be relieved without the need for open heart surgery, it is likely that pulmonary artery banding would be used more frequently in the management of infants with congenital heart disease. Such a pulmonary artery band was placed in seven 1 week old mongrel puppies by using a loop of an absorbable suture material (Vicryl). One dog died at 2 months as a result of right ventricular failure. The remaining six dogs underwent cardiac catheterization and pulmonary balloon angioplasty at 6 months of age. After measuring pulmonary artery, right ventricular and aortic pressures and performing a right ventricular angiogram, balloon angioplasty of the band site was performed. A 20 mm balloon angioplasty catheter (Medi-Tech) was used in all dogs. Balloon angioplasty decreased right ventricular pressure from 101 +/- 19 to 42 +/- 3 mm Hg (p less than 0.05) and right ventricular systolic outflow tract gradient from 59 +/- 14 to 7 +/- 2 mm Hg (p less than 0.03), and increased the size of the band site from 8.7 +/- 0.03 to 14.9 +/- 0.5 mm (p less than 0.01). All dogs were recatheterized 2 months after angioplasty and were then killed for pathologic evaluation. At follow-up catheterization, right ventricular pressure, right ventricular outflow tract gradient and pulmonary artery size at the band site remained at the values obtained immediately after angioplasty. Postmortem examination demonstrated that there was no evidence of pulmonary artery damage. Although these studies are preliminary, they suggest that a reversible pulmonary artery band can be performed.

Myocardial infarct size is smaller in dogs with pacing-induced heart failure.

OBJECTIVE: Determine if ischemic tolerance is reduced in the setting of experimental heart failure (HF). METHODS: Dogs were paced for 3 weeks at 240 BPM to induce heart failure which was confirmed with hemodynamic and echocardiographic measurements. The pacemaker was turned off 30 min prior to the ischemia study. Normal (n = 9) and HF dogs (n = 12) were anesthetized with sodium pentobarbital, instrumented for cardiovascular assessment through a left lateral thoracotomy, and myocardial blood flow was measured with radioactive microspheres. The left circumflex (LCX) artery was occluded for 90 min followed by 3 h of reperfusion. Infarct size was determined with triphenyl tetrazolium chloride staining. RESULTS: Two-dimensional echocardiograms were obtained before and after 3 weeks of pacing in the HF group. Ejection fraction was reduced from 67 +/- 1 to 32 +/- 2% (P < 0.001) and left ventricular end-diastolic volume (LVEDV) increased from 29 +/- 4 ml before pacing to 47 +/- 5 ml (P < 0.001). HF dogs were characterized by a smaller peak positive dP/dt (1110 +/- 72 vs. 2546 +/- 41 mmHg/s, P < 0.01), a greater LV end-diastolic pressure (34 +/- 3 vs. 9 +/- 2 mmHg, P < 0.01), and lower LV end-systolic pressure (99 +/- 5 vs. 130 +/- 5 mmHg, P < 0.05) compared to control dogs. Heart rate was not significantly different between the two groups throughout the experiment. More HF dogs died from ventricular fibrillation (4/12) than control dogs (1/9), but this difference was not statistically significant (P > 0.2). The LCX occlusion produced a comparable decrease in blood flow in HF and normal dogs (0.08 +/- 0.01 vs. 0.09 +/- 0.01 ml/min/g), but infarct size as a percentage of the region at risk was smaller in HF dogs compared to normal dogs (21 +/- 4 vs. 45 +/- 4%, P < 0.01). Region at risk size was also smaller in HF versus normal dogs (29 +/- 3 vs. 40 +/- 2%, P < 0.05). Accordingly, a subgroup analysis of 6 HF and 5 control dogs with similar RAR sizes (35 +/- 2% vs. 37 +/- 2%) was performed and it also demonstrated that infarct size in HF dogs was smaller than in control dogs (19 +/- 5 vs. 40 +/- 4%, P < 0.01), suggesting that disparities in risk region size did not explain the differences in infarct size. CONCLUSION: Infarct size produced by a standardized ischemia-reperfusion protocol was smaller in dogs with pacing-induced HF. The reduced extent of infarction could not be attributed to differences in collateral blood flow or the size of the region at risk. Although the hearts in HF dogs were dilated, LV systolic blood pressure and the strength of contraction were lower than controls potentially reducing myocardial oxygen demand and explaining the smaller infarct size in HF dogs. Other mechanisms, however, cannot be discounted. Thus, ischemic tolerance is not reduced and may be augmented in dogs with pacing-induced heart failure.

Detection of latent coronary stenosis in conscious dogs: regional functional and electrocardiographic responses to isoprenaline.

A conscious animal model was developed in which coronary stenosis could be produced while regional myocardial function and local surface electrocardiograms were measured. Responses to isoprenaline stress in the presence of mild (latent) coronary stenosis were then examined. In the absence of coronary stenosis, isoprenaline produced increases in regional function and no change in the surface VCG; at higher doses, increases in the endocardial ST segments occurred. After partial coronary stenosis, which produced no apparent regional dysfunction or electrocardiographic changes, isoprenaline infusion for 3 min (0.02 microgram . kg-1 . min-1) rapidly produced decreases in percentage wall thickening (average 17 +/- 4%, mean +/- SE, P < 0.01) and increases in the mean sum of VCG ST segments by 0.23 +/- 0.06 mV (P < 0.05). 1 min after stopping isoprenaline, most dogs showed further significant deterioration of both measures of ischaemia, but by 5 min there was no significant mean change from control. We conclude that in the presence of latent partial coronary stenosis, stress due to mild sympathomimetic stimulation alone can rapidly induce regional myocardial ischaemia. Deterioration of regional myocardial contractile function during such stress can provide as sensitive means of detecting latent coronary obstruction.

Regulation of blood flow to the rabbit corpus luteum: effects of estradiol and human chorionic gonadotropin.

We tested the hypothesis that estrogen and hCG can modify blood flow in the rabbit corpus luteum. Radioactively labeled microspheres were used to measure luteal blood flow in pseudopregnant rabbits in which estrogen had been withdrawn to initiate premature luteal regression and in pseudopregnant rabbits injected with hCG. Removal of estradiol-filled Silastic capsules on day 10 of pseudopregnancy caused an 80% decrease in the serum progesterone concentration within 24 h. Despite the decline in progesterone secretion, luteal blood flow remained at very high levels and was not different from that in control rabbits treated continuously with estradiol. Replacement of estradiol-filled capsules for 3 h did not change the high rate of blood flow to the corpus luteum, but blood flow in the uterus, vagina, and ovarian stroma was increased. The injection of hCG (10 IU, iv) on day 10 of pseudopregnancy caused a 3-fold increase in blood flow to the nonluteal portion of the ovary and a 3-fold increase in the serum progesterone concentration, but luteal blood flow did not change. We conclude that the acute actions of estradiol or hCG in the rabbit corpus luteum are not mediated by changes in luteal blood flow. Further, the results suggest that the luteal vasculature is regulated differently from the vasculature of other estrogen-responsive tissues and that blood flow in the nonluteal tissues of the ovary can be regulated independently of blood flow in the corpus luteum.

The relationship between myocardial blood flow and glucose uptake in ischemic canine myocardium determined with fluorine-18-deoxyglucose.

The relationship between myocardial blood flow as a marker of severity of ischemia and exogenous glucose utilization was examined following occlusion of the left anterior descending coronary artery in 10 fasted, anesthetized, open-chest dogs. Fluorine-18-fluorodeoxyglucose (FDG) was injected 10 min after the onset of ischemia and serial blood samples were obtained to measure FDG in plasma. Tracer-labeled microspheres, used to measure myocardial blood flow (MBF), were injected 10 and 40 min postocclusion. After the last microsphere injection, the heart was arrested and removed rapidly. Tissue samples of the left ventricle were obtained, weighed and FDG counts were determined. Two days later, the same samples were assayed for radioactivity from the tracer-labeled microspheres and blood flow was calculated. Thus, FDG uptake and MBF measurements were made in the same tissue samples. When normalized for variations in blood flow, there were no significant differences in FDG uptake between the subendocardial and subepicardial halves of the tissue samples. FDG uptake was relatively high and uniform in normal myocardium, paralleling the pattern of MBF. In ischemic myocardium, however, FDG uptake and MBF did not vary in parallel. In tissue samples with MBF reduced by up to 80% from control levels, relative FDG uptake increased such that absolute FDG uptake remained at normal or near normal levels. In samples with more severe ischemia, FDG uptake decreased precipitously with additional decrements in MBF. We propose that sufficient glycolytic flux may be sustained to maintain cellular viability when perfusion is above the threshold value. Below the threshold, however, irreversible changes may be initiated.

Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow.

SQ30217 is a new, technetium-99m-(99mTc) labeled perfusion agent introduced for cardiac imaging. To evaluate the myocardial tracer kinetics, 99mTc-SQ30217, was injected intracoronarily in open-chested dogs under baseline conditions and after administration of intravenous (i.v.) dipyridamole. Myocardial first-pass retention fraction averaged 0.90 +/- 0.04. Clearance of the tracer occurred in a biexponential manner. Sixty-seven percent of retained activity cleared with a half-time of 2.3 +/- 0.6 min, while the residual activity demonstrated slow clearance. The clearance rate of the rapid phase correlated with myocardial blood flow (r = 0.72, p less than 0.001). Myocardial SQ30217 clearance rate following i.v. injection as determined by dynamic imaging with tomography (SPRINT) averaged 21 +/- 4 min and increased to 13 +/- 4 min following dipyridamole. Thus, 99mTc-SQ30217 is a promising flow tracer with high initial myocardial retention and rapid tissue clearance, which allow repeated flow determinations within short time intervals using advanced SPECT technology.

End-systolic dimension-wall thickness relations during myocardial ischemia in conscious dogs. A new approach for defining regional function.

Overall and regional left ventricular (LV) function was studied during progressive coronary stenosis in conscious dogs by determining the relations at end-systole between LV pressure, chamber dimensions, and regional LV wall thickness. An index of regional wall stress was also analyzed. Using ultrasonic dimension gauges, measurements were made of LV wall thickness in control and ischemic regions, and the external long- and short-axis LV diameters were determined; an implanted micromanometer measured LV pressure. Internal LV diameters were obtained from the external diameters by subtraction of wall thickness, and the index of regional wall stress employed a thick-walled ellipsoidal model. During regional ischemia, the LV long axis at end-systole did not change, whereas the short-axis diameter progressively increased (from 24 +/- 7 mm [standard deviation] to 30 +/- 9 mm, p less than 0.001, indicating a more spherical LV shape during ischemia). The end-systolic pressure did not change, and therefore the end-systolic pressure-diameter relation shifted progressively, suggesting a global decrease in LV contactility. The end-systolic points relating LV wall thickness in the ischemic region to the end-systolic LV pressure revealed the regional nature of the abnormality, showing a progressive displacement to the left, whereas there was no significant displacement of this relation in the control region. The application of this index over a range of loading conditions during partial vena caval occlusion was illustrated. Thus, the regional end-systolic wall thickness-pressure relation provides a new index for defining the regional contractile state of the LV myocardium which is potentially load-independent and offers the possibility for echocardiographic application.

Protection of the neonatal myocardium during hypothermic ischemia. Effect of cardioplegia on left ventricular function in the rabbit.

The protective effect of cardioplegia upon neonatal myocardium during ischemia has not been clearly established. This study evaluated the effects of cardioplegia on left ventricular function in isolated working neonatal rabbit hearts (aged 1 week) subjected to 120 minutes of global ischemia at 28 degrees C. Four groups were studied: Group 1, hypothermia alone; Group 2, intermittent washout with an oxygenated noncardioplegic solution; Group 3, multidose cardioplegia; Group 4, single-dose cardioplegia. After ischemia, cardiac output was reduced to 72% +/- 5% (mean +/- standard error of the mean) of control (p less than 0.02) in Group 1 and to 56% +/- 4% in Group 2 (p less than 0.001). In contrast, there was no significant reduction from baseline cardiac output in those animals receiving cardioplegic solution (Group 3, 93% +/- 6%, and Group 4, 97% +/- 4%). Group 2 hearts demonstrated significantly worse recovery of cardiac output and stroke volume than all other groups. After ischemia, the first derivative of left ventricular pressure fell to 73% +/- 13% of control in Group 1 (p less than 0.1) and to 89% +/- 5% in Group 2 (p less than 0.05). However, the first derivative of left ventricular pressure was restored to control values in Group 3 (118% +/- 11%) and Group 4 (114% +/- 9%). When compared to baseline, creatine kinase was higher 30 minutes after reperfusion in Group 1 (40 +/- 8 versus 143 +/- 32 IU/L/gm, p less than 0.05) and in Group 2 (39 +/- 7 versus 163 +/- 33 IU/L/gm, p less than 0.05). Creatine kinase remained unchanged from baseline in Groups 3 and 4. This study demonstrates excellent preservation of left ventricular function in the neonatal rabbit heart protected with cardioplegic solution. In contrast, neither hypothermia alone nor intermittent washout with an oxygenated noncardioplegic solution was effective in preventing myocardial dysfunction. As in adults, the administration of cardioplegic solution preserves ventricular function during ischemia in neonatal hearts.

Flavone improves functional recovery after ischemia in isolated reperfused rabbit hearts.

The effects of flavone (2-phenyl-1,4-benzopyrone), a modulator of the cytochrome P-450 monooxygenase system, on myocardial postischemic reperfusion recovery were examined in the present study. Left ventricular functional recovery was evaluated in isolated, crystalloid-perfused rabbit hearts after 2 hours of modestly hypothermic (34 degrees C) global ischemia. Four groups (n = 8 in each group) were studied and compared: a vehicle control group, a second group pretreated with flavone (8 x 10(-6) mol/L) before ischemia, a third group pretreated with flavone followed by SKF 525-A (1.7 x 10(-5) mol/L), an inhibitor of cytochrome P-450, and a fourth group pretreated with flavone followed by indomethacin (1 x 10(-6) mol/L), an inhibitor of cyclooxygenase. At 15, 30, and 45 minutes after reperfusion, recovery of left ventricular developed pressure in the control group averaged (mean +/- standard deviation) only 2.60% +/- 12.7%, 35.5% +/- 15.0%, and 42.9% +/- 13.5% of baseline, respectively. In the flavone-treated group, recovery was significantly better, averaging 67.7% +/- 10.7%, 73.9% +/- 9.3%, and 73.6% +/- 7.6% of baseline at the same time periods. Recovery of peak positive rate of pressure rise in the control group averaged 27.4% +/- 15.2%, 38.6% +/- 19.2%, and 45.4% +/- 18.6% of baseline at 15, 30, and 45 minutes of reperfusion, respectively. In the flavone-treated group recovery values were significantly higher, averaging 67.8% +/- 9.6%, 77.3% +/- 8.5%, and 77.0% +/- 9.0% of baseline. End-diastolic pressures were significantly lower in the flavone-treated group compared with the control group at all reperfusion time points. Myocardial oxygen consumption was significantly higher in the flavone-treated group at 30 and 45 minutes of reperfusion, as well. The improvement resulting from flavone infusion was abolished completely by SKF 525-A, providing support for the interpretation that the effects of flavone were mediated through the cytochrome P-450 system. The cyclooxygenase inhibitor indomethacin midly attenuated the effects of flavone pretreatment, suggesting that the effects of flavone were only minimally related to metabolites of cyclooxygenase. We conclude that pretreatment with flavone represents a promising approach to myocardial protection that may be due to modulation of the myocardial cytochrome P-450 system.

The regional effect of retrograde cardioplegia in areas of evolving ischemia.

Retrograde cardioplegia (RCP) is often used for myocardial protection during coronary bypass grafting, but the regional effect of RCP in areas of evolving ischemia is unknown. We examined the functional and metabolic indices of regional myocardial preservation following acute coronary occlusion with evolving ischemia in a canine model. Following the institution of 37 degrees C cardiopulmonary bypass in 14 dogs, the left anterior descending artery (LAD) was occluded for 15 min. The hearts were then subjected to 90 min of cardioplegic arrest (12 degrees C, 15 mL/kg every 30 min). Seven had antegrade cardioplegia (ACP) alone, while seven had ACP until arrest, then RCP. No topical cooling was used. The LAD occlusion was released after the first bolus of cardioplegia. Regional temperature and pH were measured in the LAD and circumflex (nonischemic) distributions. After 90 min of ischemia and 30 min of reperfusion, all dogs were weaned from bypass. Postischemic function was determined globally by the return of developed pressure (%dP/dt) and regionally by ultrasonic wall crystals. End-ischemic ATP preservation in the LAD distribution was assessed by HPLC (mm ATP/mg protein). Results show that regional functional and metabolic indices were better maintained with RCP in the ischemic LAD distribution. Although only moderate reduction of global function was seen with ACP, the severe reduction noted in LAD regional wall motion with ACP reflects poor regional protection that can be significantly improved in evolving ischemia with RCP.

Augmenting intracellular adenosine improves myocardial recovery.

The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. Isolated adult rabbit hearts were subjected to 120 minutes of mildly hypothermic ischemia (34 degrees C) with modified St. Thomas' Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution or by inhibiting adenosine degradation with 2-deoxycoformycin, a noncompetitive inhibitor of adenosine deaminase. Four groups of hearts were studied: (1) control (n = 23)--cardioplegia alone; (2) adenosine group (n = 10)--adenosine 200 mumol/L added to the cardioplegic solution; (3) 2-deoxycoformycin group (n = 8)--2-deoxycoformycin 1 mumol/L added to the cardioplegic solution; and (4) a combined adenosine/deoxycoformycin group (n = 10). Recovery of developed pressure 45 minutes after reperfusion in the control group averaged only 38% +/- 4% of baseline values. Significantly better recovery was evident in the adenosine (66% +/- 7%), deoxycoformycin (59% +/- 2%), and adenosine/deoxycoformycin (75% +/- 2%) groups. The slope of the relationship between end-diastolic pressure and volume was used as an index of diastolic stiffness. The slope averaged 85 +/- 2 mm Hg/ml in the control group 45 minutes after reperfusion, significantly higher than that in the adenosine (31 +/- 6), deoxycoformycin (75 +/- 5), and adenosine/deoxycoformycin (58 +/- 5) groups; this suggests better diastolic function in the adenosine-augmented groups. During ischemia, adenosine levels were significantly elevated in the adenosine-augmented groups, whereas adenosine triphosphate decreased equally in all four groups, which indicates that augmenting myocardial adenosine had no effect on depletion of adenosine triphosphate during ischemia. After reperfusion, adenosine triphosphate levels were depressed in the control group but increased in the other groups above baseline values, which suggests that improvement in functional recovery was due to accelerated repletion of adenine nucleotide stores in the adenosine-augmented groups.

Recovery of the neonatal heart after normothermic ischemia. Effect of oxygen and catalase.

The objective of this study was to determine the effect of oxygen and the oxygen radical-scavenging enzyme catalase on the neonatal rabbit heart exposed to global ischemia. The experiments were performed with an isolated neonatal (7 to 10 days of age) working heart model in which normothermic (37 degrees C) ischemia was produced for 60 minutes. Left ventricular developed pressure, ratio of change of ventricular pressure to change in time, and aortic flow were measured before ischemia and 30 minutes after reperfusing the hearts with physiologic saline solution. In the control group (ischemia only), developed pressure and ratio of change of ventricular pressure to change in time recovered to 27% +/- 3% (mean +/- standard error of the mean) and 24% +/- 7% of baseline; the hearts were incapable of ejecting (aortic flow = 0). Treatment of hearts before and after ischemia with catalase (150 units/ml of perfusate) was studied in a second group (control plus catalase), but functional recovery (developed pressure = 32% +/- 1%; ratio of change of ventricular pressure to change in time = 24% +/- 2%, and aortic flow = 0) was not significantly different from the control group. The effect of washout midway through the ischemic period with a low oxygen (oxygen concentration less than 35 mm Hg) solution was measured in a third group (hypoxic physiologic saline solution). Functional recovery (developed pressure = 13% +/- 3%; ratio of change of ventricular su pressure to change in time = 13% + 2%; aortic flow = 0) was not significantly different from the control and control plus catalase groups. In marked contrast were the effects of washout with an oxygenated (oxygen concentration greater than 500 mm Hg) solution (oxygenated physiologic saline solution) in which functional recovery (developed pressure = 78% +/- 3%; ratio of change of ventricular pressure to change in time = 80% +/- 3%; aortic flow = 39% +/- 9%) was significantly better than in the control, control plus catalase, and hypoxic physiologic saline solution groups. Use of modified St. Thomas' Hospital cardioplegic solution (cardioplegic solution group) during the ischemic period also resulted in substantial functional recovery (developed pressure = 80% +/- 3%; ratio of change of ventricular pressure to change in time = 78% +/- 5%; aortic flow = 64% +/- 7%) that did not differ significantly from that in the oxygenated physiologic saline solution group.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia.

The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function.

Distribution of cardioplegic solution infused antegradely and retrogradely in normal canine hearts.

The adequacy of retrograde delivery of cardioplegic solution to the right ventricle and interventricular septum is controversial. To address this issue quantitatively, we infused blood cardioplegic solution labeled with radioactive microspheres (15 microns diameter) into the coronary sinus (n = 8 dogs) at a pressure of 51 +/- 1 mm Hg (mean +/- standard error of the mean) to be compared with the same quantity of labeled cardioplegic solution (20 ml/kg) delivered through the aorta (n = 6 dogs) at 97 +/- 7 mm Hg. Both methods of delivery produced cardiac arrest, but retrograde infusion required a significantly longer time to complete the infusion (6.2 +/- 0.8 minutes versus 1.5 +/- 0.1 minutes, p less than 0.01). Greater than 99% of the microspheres passing through the vasculature of the left ventricle were trapped in the left ventricular myocardium with antegrade infusion, and the distribution of the cardioplegic solution was uniform. Antegrade delivery (cardioplegic flow x infusion time) averaged approximately 3.0 to 4.0 ml/gm, except at the apex, where delivery averaged approximately 2.0 ml/gm. With retrograde infusion, 93% of the microspheres perfusing the left ventricle were trapped and delivery of the cardioplegic solution was not uniform. In the anterolateral free wall, delivery of cardioplegic solution averaged between 1.5 and 2.9 ml/gm (p less than 0.001 compared with antegrade) and only 0.6 to 0.8 ml/gm in the posteroseptal region of the basal left ventricle (p less than 0.001 compared with the antegrade group and anterolateral samples of the retrograde group). In the middle portion of the right ventricle, antegrade trapping of microspheres was 99% and delivery of cardioplegic solution averaged approximately 2.0 ml/gm. With retrograde delivery, only 16.5% (range 11.8% to 26.0%) of the microspheres passing through the right ventricular vasculature were trapped in the right ventricular myocardium, which indicates that substantial shunting had occurred. Corrected for the high shunt fraction, retrograde delivery of cardioplegic solution to the middle portion of the right ventricle averaged only 0.5 ml/gm (p less than 0.01). Retrograde delivery to the atrial septum and right atrium was also low. Because retrograde delivery of cardioplegic solution was markedly nonuniform, we conclude that inadequate cardioplegic delivery to the middle portion of the right ventricle and posteroseptal portion of the left ventricle could result with cardioplegic infusion through the coronary sinus.

The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart.

Neonatal and adult myocardium respond differently to ischemia. In addition, the neonatal heart possesses a limited preload reserve. The effect of uninterrupted hypothermic ischemia on recovery of left ventricular function and preload reserve was studied in two groups of isolated rabbit hearts: group 1 (neonates, n = 8), 7 to 10 days old; group 2 (adults, n = 15), 6 to 12 months old. Peak left ventricular systolic pressure, the first derivative of left ventricular systolic pressure, and heart rate were measured at left ventricular pressures of 0, 5, 10, and 15 mm Hg before and after 120 minutes of global ischemia at 27 degrees C. Before ischemia, left ventricular systolic pressure increased significantly at each increment of left ventricular end-diastolic pressure for both groups of hearts. After hypothermic ischemia, recovery of left ventricular systolic pressure was significantly reduced at each level of left ventricular end-diastolic pressure among neonatal hearts (range 75% to 79% of control values). The postischemic recovery of left ventricular systolic pressure in the adult hearts was markedly reduced from baseline values (range 43% to 53% of control values) and was significantly worse than that of neonatal hearts at each level of left ventricular end-diastolic pressure (p less than 0.001). Both groups were able to respond to increasing preload after ischemia. The slope of the curve describing the relationship between left ventricular end-diastolic pressure and percent recovery of left ventricular systolic pressure was not different from zero for neonatal hearts but was significantly greater than zero among the adults (0.22 +/- 0.21 versus 0.73 +/- 0.07, p = 0.0056). After ischemia, the first derivative of left ventricular systolic pressure fell significantly from control values among neonatal hearts (71% of control values). The reduction was considerably greater, however, among the adult hearts (54% of control values). These data indicate that the neonatal heart recovers systolic function better than the adult heart after global ischemia with moderate hypothermia.