How to cite this article:Luisetto Mauro, Farhan Ahmad Khan, Ghulam Rasool Mashori. New Pharmacological Strategies in some Heart Disease Under
a Toxicological Point of View. Open Acc J of Toxicol. 2018; 2(4): 555591. DOI: 10.19080/OAJT.2018.02.555591
Today we need to introduce new approach in some cardiovascular pathology and to do this we think is useful to use a toxicological approach, new delivery systems and new diagnostic strategies. (This paper is produced under a pharmaceutical-toxicological approach.)
We can think a new method in heart disease clinical staging strategy. New tests that can make possible to stress cardiac metabolism in normal, lowland high working conditions or in para-phisio-pathological conditions but in local place (heart situation and not in plasma in example). We think that this new methods can be useful in much heart disease and condition to prevent some events. (Heart attacks, ischemic disease, aritmia, heart failure, transplants, sports and so on). Every bio-medical discipline has specific diagnostic discipline, but it can be useful to translate the various diagnostic system strategies from a discipline to other: this make possible to observe phenomena with a different point of view .
“We must consider an endogenous local toxicology aspect time related to verify some pathologic process and phenomena under a new useful light. In some time related CV local metabolic-
catabolic-toxic status we can observe some cellular effect resulting in global organ- apparatus failure. The time involved (and kinetics aspect) in resolve some temporary metabolic-catabolic- electric gradients or the global velocity involved in this process can be fundamental to consider (too rapid evolution or too slow reduction in balancing -equilibrates some physiologic systems)” .
In example what happen in SCD in untrained?  Why physical training can reduce this event (SCD)? We can think a condition of ENDOGENUS toxicity time- KINETICKS related. So We think in this kind of condition is relevant to better observe the time related endogenous intra- toxicity situation involved in some Metabolic- catabolic –electrical cell membrane and other.
For example involved in some heart aritmia, epilectic status, septic shock and other situation high time related (ischemic coronaric spasm etc). In embryology, oncology, toxicology, pathology some heart and brain disease the time is relevant factors added to endogenous local- micro environment and inter- cellular communication (crisis). We can consider an intra- local toxicology aspect time related to better verify some pathologic process under a new light .
In actual pharmacological therapy we can see that some drugs can be added to other medical instruments to improve their activity: in example we can see medicated stent for some coronary disease, or hormonal medical devices used in pregnancy prevention, but other example is known today. In example Carmustine wafer is delivered by delivery systems in some brain cancer and radioactive seed implants in prostatic cancer. Ocular intra virtual implants for some macular degeneration (MABS or cortisones) other implant delivery systems drugs, naltrexone
implant for opiate dependence.
In example MABS linked to radioactive isotopes in some
relapse of severe Hodgkin disease but many other examples we
can see in therapy used today. So we can think that other chronic
conditions can be treated using a combination of drugs with
other instrument to improve the clinical outcomes. This is to
make possible that the ERLICH MUGIC BULLETS can act in the
right site reducing the side effect. In example today we can see
various medical interventional radiological strategy to treat in
coronary and heart disease with medicate stents positioning or
to local use of contrast agents or other valve surgery procedures
with global good clinical results .
“We can say that under the light of the article finded in this
paper but also to other works published we can think a new
system “to regenerate” a valve tissue calcified. We think that
adding 3 strategies medical interventional radiological strategy,
pharmacological agent like complexant or other molecule with
a delivery system we can have relevant effect reducing global
“The causes and the mechanisms underlying the development
of CAS are still poorly defined and are likely multifactorial. In
the 1980s, the autonomic nervous system was found to play
an important role in the pathophysiology of CAS. In the 1990
YEARS, some factors as flogosis inflammation, endothelial vessel
dysfunction, oxidative stress agents, respiratory alkalosis and
magnesium (Mg) deficiency were identified as predisposing
factors In the late 1990s and early 2000s, genetic mutations
were found to be associated with CAS. Nonetheless, coronary
vascular smooth muscle cell hyper-reactivity seems to constitute
the substrate for CAS” .
“Sudden death is an important but widely underrecognized
consequence of stroke. Acute stroke can disturb
central autonomic control, resulting in myocardial injury,
electrocardiographic abnormalities, cardiac arrhythmias, and
ultimately sudden death. Experimental - clinical objective
evidence suggests that autonomic imbalance situations is more
frequent after brain infarcts involving the insular cortex region,
crucial for the control of autonomic functions level (sympathetic
– parasympathetic). Cardiovascular comorbidities increase the
risk of cardiac morbidity and mortality after stroke . Thus,
many sudden deaths and serious non-fatal cardiac events after
stroke are probably due to an interaction between cardiovascular
and neurological causes. The exact mechanisms leading to
sudden death remain incompletely understood. Further research
is needed to investigate the autonomic consequences of acute
stroke and to identify patients at high risk of sudden death” .
Results of the first large-scale randomized trial of this
treatment. “TACT a large-scale clinical trial of chelation therapy
for some atherosclerotic coronary pathology, found that EDTA
(a chelation therapy) reduced the risk of a composite of adverse
CV clinical outcomes, especially among patients with diabetes.
Before disodium EDTA chelation can take its place among other
accepted therapies in the routine care of post-MI patients,
however, it is important that further replicative and mechanistic
clinical trials be performed” .
Evidence that human cardiac dysfunction is associated with
excess lipid; Clinical data show that both obesity and diabetes
markedly increase risk of heart failure even in the absence of
ischemic vascular disease. The molecular mechanisms could be
either increased the lipid uptake or an impaired mitochondrial
oxidative function leading to accumulation of molecules of TGs
and toxic lipid species such as ceramides, which cause myocyte
loss through apoptosis, induction of iNOS and pro-hypertrophic
signaling. Therefore, the specific form of excess cardiac lipid
products- compounds their cellular compartmentalization and
storage form (lipid droplets), and the specific cause of CHF heart
failure are likely to determine the importance of lipotoxicity in
human disease. Studies of human HAERT function / metabolism
rely on imaging methods (relatively non-invasive). PET scanning
DIAGNOSTIC assesses the uptake of various tracers into the
heart (well standardized for the glucose and FFA uptake).
Myocardial PET imaging technique has consistently showed
the increased FFA uptake and oxidation, impaired glucose
uptake, in diabetic patients with normal systolic and mildly
impaired diastolic function.
In Recent time RM magnetic resonance protocols have
been developed to track TG metabolism such as 1H magnetic
resonance spectroscopy (MRS). Although hypertension and
coronary artery disease are common in obese and diabetic
patients, reduced heart function independent of these underlying
disorders may relate to toxicities from excess metabolic
substrates and defective insulin action. Some studies in patients
with obesity and diabetes correlated TG accumulation with left
ventricular hypertrophy . More TG has also been found in
failing hearts of patients with obesity or diabetes at the time
of transplantation . Reducing plasma lipids to reduce lipid
uptake and converting oxidation to more glucose and less FA
might be a method to treat patients with lipotoxic and ischemic
heart failure. Agents that inhibit FA oxidation have been used for
CV diseases are a leading cause of morbidity and mortality in
most developed countries of the world.
DRUGS illicit drugs and toxins can significantly contribute
to the overall cardiovascular burden. The compounds are in
this paper classified into agents that have significant effects
on the heart, blood vessels, or both. The mechanism(s) of toxic
action are discussed and the treatment modalities are briefly
mentioned in relevant cases.
Due to the large number of clinically relevant compounds
and molecules discussed, this paper could be of interest to a
broad audience including pharmacologists toxicologists, clinical pharmacists, physicians, and medicinal chemists, medical
laboratory professionals and other particular emphasis is given
to the clinically relevant topics and interesting including the
cardiovascular toxicity of illicit sympathomimetic drugs (e.g.,
cocaine, amphetamines, cathinones), drugs that prolong the QT
interval, antidysrhythmic drugs, digoxin and others molecules,
cardio-active steroids, beta blockers, CA++ channel blockers,
female hormones, FANS nonsteroidal anti-inflammatory, and
anticancer compounds as anthracyclines and targeted therapy
interfering with the HER2 or the vascular endothelial growth
factor pathway . Diabetes and heart failure PATHOLOGY
commonly coexist and portend worsened prognosis than either
disease alone .
Observing the reported literature in some heart disease we
have see that some phenomena are deeply involved: Kinetics
and gradients in metabolism catabolism time related toxic like
effect electrical cell membrane status, smooth vascular muscle
cell hyper-reactivity platelet iperactivations, central autonomic
control after acute stroke great electrolytes unbalances et other.
We think that using and antidotes- toxicological approach new
delivery systems and new diagnostic approach in ranking the
clinical risk we can obtain new Pharmacological strategies
useful in some cardiovascular conditions. To prevent some kind
of heart disease we think can be useful introduce new diagnostic
strategy to verify in stressing conditions the local metabolic heart
performance in example in young or before high sports activities.
Can we consider a sort of chronic endogenous poisoning some
cardiovascular disease as atherosclerotic pathology or diabetes
type II or other?
We think that a deep knowledge in the right mechanism(s) of
toxic action in some cardio vascular conditions using a specific
toxicological approach can produce new research hypothesis to
be verified for new pharmacological way to be introduced.